Primary Coenzyme Q10 Deficiency
Primary coenzyme Q10 (CoQ10, ubiquinone) deficiency is a clinically and genetically heterogeneous group of autosomal recessive mitochondrial disorders caused by biallelic pathogenic variants in nuclear genes required for endogenous CoQ10 biosynthesis. Reduced tissue CoQ10 impairs electron transfer through the mitochondrial respiratory chain (between complexes I/II and complex III), compromises oxidative phosphorylation, and disrupts additional CoQ-dependent processes (antioxidant defense, pyrimidine and sulfide metabolism, ferroptosis protection), producing multisystem, high-energy-organ disease. Phenotypes range from lethal neonatal encephalomyopathy to childhood/adult-onset cerebellar ataxia, with prominent renal (steroid-resistant nephrotic syndrome), neurologic, cardiac, and sensorineural manifestations that vary by causal gene. It is one of the few potentially treatable mitochondrial disorders: high-dose oral CoQ10 supplementation can reverse or prevent renal disease and ameliorate neurologic features if given before irreversible organ injury.
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Classifications
Harrison's Part
Mechanistic Nosology
Inheritance
1
Autosomal Recessive
HP:0000007
Show evidence (1 reference)
"Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway."
Primary CoQ10 deficiency is caused by biallelic pathogenic variants in CoQ10 biosynthesis genes, inherited in an autosomal recessive pattern.
Subtypes
10
COQ2-related (CoQ10 deficiency-1)
MONDO:0011829
COQ2 (4-hydroxybenzoate polyprenyltransferase) was the first CoQ10 biosynthesis gene linked to disease. The phenotype spans infantile multisystem encephalomyopathy with nephrotic syndrome to isolated steroid-resistant nephropathy. This form is curated in full as its own dismech entry, COQ2-Related_Primary_Coenzyme_Q10_Deficiency, and is cross-referenced here rather than duplicated.
Show evidence (2 references)
"The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy."
COQ2 was the first identified primary CoQ10 biosynthesis gene, causing encephalomyopathy with nephrotic syndrome. The quoted sentence is this PDSS2 report's summary of the earlier COQ2 patients rather than its own result.
"In the second family, direct sequencing of OH-benzoate polyprenyltransferase (COQ2), the human ortholog of the yeast COQ2 gene, identified a single base pair frameshift deletion resulting in a premature stop codon (c.1198delT, N401fsX415)."
An independent family with a biallelic truncating COQ2 variant, naming the enzyme activity COQ2 contributes to the pathway.
COQ4-related (lethal neonatal encephalomyopathy)
MONDO:0014562
COQ4 variants cause an autosomal recessive lethal neonatal mitochondrial encephalomyopathy with hypotonia, encephalopathy, seizures, cerebellar atrophy, cardiomyopathy, and lactic acidosis; a founder mutation occurs in the Ashkenazi Jewish population, and a high incidence is reported in southern China. This form is curated in full as its own dismech entry, COQ4-Related_Neonatal_Encephalomyopathy, and is cross-referenced here rather than duplicated.
Show evidence (1 reference)
"Mutations in COQ4 cause an autosomal recessive lethal neonatal mitochondrial encephalomyopathy associated with a founder mutation in the Ashkenazi Jewish population."
COQ4 variants produce a severe lethal neonatal encephalomyopathy form of primary CoQ10 deficiency.
COQ5-related (CoQ10 deficiency-9)
MONDO:0033615
COQ5 encodes a methyltransferase of the CoQ10 biosynthetic pathway. Biallelic COQ5 variants were reported in three siblings with cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures and cognitive disability, whose blood and muscle CoQ10 were reduced and who improved on CoQ10 supplementation. ClinGen grades the gene-to-mitochondrial-disease relationship Moderate rather than Definitive, on two probands.
Show evidence (4 references)
"Whole-exome and subsequent whole-genome sequencing identified biallelic duplications in the COQ5 gene, leading to reduced levels of CoQ10 in peripheral white blood cells of all affected individuals and reduced CoQ10 levels in the only muscle tissue available from one affected proband."
Establishes biallelic COQ5 variants as a cause of measured CoQ10 deficiency in patients.
"This is the first report of primary CoQ10 deficiency caused by loss of function of COQ5, with delineation of the clinical, laboratory, histological, and molecular features, and insights regarding targeted treatment with CoQ10 supplementation."
The authors classify the COQ5 phenotype as primary CoQ10 deficiency and state the mechanism as loss of function.
"CoQ10 supplementation led to clinical improvement and increased the concentrations of CoQ10 in blood."
Source for the treatment response recorded in this subtype description.
+ 1 more reference
COQ6-related (SRNS with sensorineural deafness)
MONDO:0013836
COQ6 (CoQ10 biosynthesis monooxygenase 6) mutations produce early-onset steroid-resistant nephrotic syndrome with sensorineural deafness, an oto-renal phenotype reflecting COQ6 expression in podocytes and inner-ear stria vascularis. This form is curated in full as its own dismech entry, COQ6-Related_Steroid-Resistant_Nephrotic_Syndrome, and is cross-referenced here rather than duplicated.
Show evidence (1 reference)
"Each mutation was linked to early-onset SRNS with sensorineural deafness."
COQ6 mutations cause steroid-resistant nephrotic syndrome with sensorineural deafness.
COQ8A/ADCK3-related (cerebellar ataxia)
MONDO:0012784
The COQ8A (ADCK3) cerebellar-ataxia form (primary CoQ10 deficiency-4, ARCA2/SCAR9) is curated as a separate dismech entry (Autosomal_Recessive_Ataxia_Due_to_Ubiquinone_Deficiency). It is cross-referenced here as an already-split member and is not duplicated in this umbrella entry.
Show evidence (1 reference)
"Thus far, 11 disease genes are known (PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9 and HPDL)."
COQ8A is one of the recognized primary CoQ10 biosynthesis disease genes; its cerebellar-ataxia form is curated in a dedicated dismech entry.
COQ8B/ADCK4-related (SRNS)
MONDO:0014257
COQ8B (ADCK4) mutations cause steroid-resistant nephrotic syndrome, typically with later (childhood/adolescent) onset than COQ6, and may be partially responsive to CoQ10 supplementation. MONDO files this form under familial idiopathic steroid-resistant nephrotic syndrome as nephrotic syndrome type 9, not beneath the coenzyme Q10 deficiency umbrella, so the subtype term here is the renal-nosology class rather than a numbered CoQ10 deficiency class.
Show evidence (2 references)
"Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families."
COQ8B/ADCK4 mutations cause steroid-resistant nephrotic syndrome through disrupted CoQ10 biosynthesis.
"COQ8B | HGNC:19041 | mitochondrial disease | MONDO:0044970 | AR | Definitive | SOP9 | Mitochondrial Diseases Gene Curation Expert Panel"
ClinGen grades COQ8B Definitive for autosomal recessive mitochondrial disease, and lumps the COQ8B renal and mitochondrial presentations into one disease entity.
COQ7-related (CoQ10 deficiency-8)
MONDO:0014754
COQ7 encodes the mitochondrial demethoxyubiquinone hydroxylase of the CoQ10 biosynthetic pathway. Two clinical presentations are described: a neonatal-onset form with severe neuromuscular, cardiorespiratory and renal involvement, and a late-onset form with progressive neuropathy and lower-limb weakness. MONDO places the COQ7 distal hereditary motor neuronopathy class MONDO:0957874 beneath this numbered form; that late-onset neuropathy is treated in dismech as a differential_diagnoses row on Distal_Hereditary_Motor_Neuronopathy_Type_9 rather than as a separate entry.
Show evidence (2 references)
"We report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB."
The first reported patient with primary CoQ deficiency caused by a biallelic COQ7 variant.
"The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involvement and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay."
Delineates the two COQ7 clinical presentations recorded in this subtype description.
COQ9-related (neonatal encephalomyopathy)
MONDO:0013840
COQ9 deficiency causes a severe neonatal-onset encephalomyopathy; the Coq9 knockout mouse recapitulates encephalopathy with cerebral gliosis and spongiosis. The index patient presented with neonatal lactic acidosis and went on to develop intractable seizures, global developmental delay, hypertrophic cardiomyopathy and renal tubular dysfunction, which are the features MONDO's label for this numbered form names.
Show evidence (3 references)
"Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of COQ9, leading to the truncation of 75 amino acids."
Identifies the biallelic truncating COQ9 variant in the index patient with primary CoQ10 deficiency.
"We genotyped a patient with primary coenzyme Q(10) deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction."
Source for the clinical course recorded in this subtype description.
"COQ9 | HGNC:25302 | mitochondrial disease | MONDO:0044970 | AR | Definitive | SOP10 | Mitochondrial Diseases Gene Curation Expert Panel"
ClinGen grades COQ9 Definitive for autosomal recessive mitochondrial disease.
PDSS1-related (CoQ10 deficiency-2)
MONDO:0013837
PDSS1 encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ10 biosynthetic pathway responsible for assembly of the polyisoprenoid side chain. MONDO's label for this numbered form names an encephaloneuropathy with deafness, obesity and valvulopathy; the family cited below presented with sensorineural deafness followed by optic atrophy.
Show evidence (3 references)
"Sequencing of PDSS1 identified a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E)."
The first reported biallelic PDSS1 variant in a family with CoQ10 deficiency.
"Here we describe two young sisters with sensorineural deafness followed by optic atrophy, due to a novel homozygous pathogenic variant in PDSS1."
An independent PDSS1 family, and the source for the sensory presentation recorded in this subtype description.
"PDSS1 | HGNC:17759 | mitochondrial disease | MONDO:0044970 | AR | Moderate | SOP10 | Mitochondrial Diseases Gene Curation Expert Panel"
ClinGen grades PDSS1 Moderate rather than Definitive for autosomal recessive mitochondrial disease.
PDSS2-related (Leigh syndrome with nephropathy)
MONDO:0013838
PDSS2 encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of CoQ10 biosynthesis. Pathogenic variants cause severe Leigh syndrome with nephrotic syndrome and CoQ10 deficiency in muscle and fibroblasts.
Show evidence (2 references)
"Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ(10) biosynthetic pathway."
PDSS2 mutations cause Leigh syndrome with nephropathy and CoQ10 deficiency.
"PDSS2 | HGNC:23041 | Leigh syndrome | MONDO:0009723 | AR | Moderate | SOP7 | Mitochondrial Diseases Gene Curation Expert Panel"
ClinGen grades PDSS2 Moderate, and records the gene against Leigh syndrome rather than against a numbered CoQ10 deficiency class.
Pathophysiology
6Defective Polyisoprenoid Side-Chain Assembly and Attachment
The first steps of CoQ10 biosynthesis build the polyisoprenoid tail and attach it to the 4-hydroxybenzoate ring. Only three of the disease genes act here: PDSS1 and PDSS2 each encode a subunit of the decaprenyl diphosphate synthase that supplies the side chain, and COQ2 is the polyprenyltransferase that joins it to the ring. Biallelic defects in this segment therefore block CoQ10 assembly at its earliest committed step, and the reported phenotypes of this segment include prominent visual involvement.
Downstream
Failure to assemble or attach the polyisoprenoid side chain blocks CoQ10 production at the earliest committed step.
Show evidence (4 references)
"Only three enzymes (PDSS1, PDSS2 and COQ2) are required for assembly and attachment of the polyisoprenoid side chain."
Defines the three genes that act at this segment of the pathway, which is the gene set bound on this node.
"The PDSS1 gene encodes prenyl diphosphate synthase subunit 1, an enzyme that supplies decaprenyl diphosphate, the precursor for the side chain of the isoprenoid quinone Coenzyme Q10 that functions as a mobile electron carrier in the respiratory chain, as well as other mitochondrial functions..."
Names the decaprenyl diphosphate synthase activity bound on this node and its role in supplying the CoQ10 side chain.
"In the second family, direct sequencing of OH-benzoate polyprenyltransferase (COQ2), the human ortholog of the yeast COQ2 gene, identified a single base pair frameshift deletion resulting in a premature stop codon (c.1198delT, N401fsX415)."
Names the 4-hydroxybenzoate polyprenyltransferase activity bound on this node, and the biallelic COQ2 defect that abolishes it.
+ 1 more reference
Defective Benzoquinone Head-Group Modification
Most of the CoQ10 biosynthesis enzymes act after side-chain attachment, on the benzoquinone ring, and may assemble into resolvable domains described as COQ complexes. COQ4, COQ5, COQ6, COQ7 and COQ9 act in this segment: COQ4 is the zinc-dependent C1 decarboxylase, COQ5 the pathway's C-methyltransferase, COQ6 its flavin-dependent ring monooxygenase, COQ7 the NADH-dependent demethoxyubiquinone hydroxylase, and COQ9 a lipid-binding protein that presents its bound lipid to COQ7. Biallelic defects in this segment therefore block CoQ10 maturation after the side chain has been attached.
Downstream
Failure to complete benzoquinone ring modification leaves CoQ10 unfinished and reduces mature CoQ10.
Show evidence (9 references)
"The majority of these enzymes are responsible for modifications of the CoQ-head group (benzoquinone ring)."
Establishes head-group modification as the segment most of the CoQ10 biosynthesis enzymes act in.
"The head-modifying enzymes may assemble into resolvable domains, representing COQ complexes."
Source for describing this segment's enzymes as assembling into COQ complexes.
"Biallelic pathogenic variants in COQ7, encoding mitochondrial 5-demethoxyubiquinone hydroxylase, have been reported in nine patients from seven families."
Names the demethoxyubiquinone hydroxylase activity bound on this node and the gene that carries it.
+ 6 more references
Defective COQ8 Kinase Support of CoQ10 Biosynthesis
COQ8A and COQ8B are closely similar atypical kinases that support the CoQ10 biosynthetic machinery rather than being assigned a named chemical step of the pathway. COQ8B localises to the mitochondrial matrix of kidney podocytes and interacts with pathway members including COQ6 and COQ7, and COQ8A was established as a pathway participant before COQ8B was identified. Loss of COQ8B reduces cellular CoQ10 in patient-derived cells.
Downstream
Loss of COQ8 kinase support of the biosynthetic machinery reduces cellular CoQ10.
Show evidence (6 references)
"Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates"
Biochemistry of COQ8A and its yeast orthologue Coq8p shows ATPase activity rather than canonical protein kinase activity, which is why the node binds ATP hydrolysis activity rather than a protein kinase term.
"Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions."
Places COQ8A's support role at the level of the CoQ biosynthesis complex, as the node description states.
"The COQ8B gene encodes the COQ8B protein, which is an atypical kinase that is expressed in the podocytes of the kidney and localizes to the mitochondrial matrix, where it participates in coenzyme Q10 synthesis."
Source for describing COQ8B as an atypical kinase participating in CoQ10 synthesis, and for the podocyte cell type bound on this node.
+ 3 more references
Defective CoQ10 Biosynthesis
Biallelic pathogenic variants in any of the nuclear CoQ10 biosynthesis genes (PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9) reduce endogenous CoQ10 production, lowering tissue and cellular CoQ10 levels. This is the shared upstream lesion across all primary CoQ10 deficiency subtypes.
Downstream
Reduced CoQ10 impairs electron transfer in the respiratory chain.
Show evidence (1 reference)
"In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status."
Defects in any of the CoQ10 biosynthesis genes reduce functional CoQ10, the shared upstream defect.
Impaired Respiratory Chain Electron Transport
CoQ10 normally shuttles electrons from respiratory chain complexes I and II to complex III. Reduced CoQ10 impairs this electron transfer, decreasing oxidative phosphorylation and ATP synthesis, biochemically detectable as reduced combined complex I+III and II+III activities.
Downstream
Energy failure combined with loss of CoQ10 antioxidant and redox functions drives multisystem injury.
Show evidence (1 reference)
"Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III."
CoQ10 transfers electrons from complexes I and II to complex III; its deficiency impairs respiratory electron transport.
Loss of Antioxidant Defense and Multisystem Energy Failure
Beyond bioenergetics, CoQ10 is a lipid-soluble antioxidant and supports redox homeostasis, ferroptosis defense, and sulfide oxidation. Combined energy failure and loss of antioxidant/redox protection produce multisystem injury, with the nervous system, kidney, heart, and sensory organs particularly vulnerable. Neurologic injury involves neuronal death, neuroinflammation, and cerebral gliosis.
Downstream
Neuronal death, neuroinflammation and gliosis in the CoQ10-deficient nervous system present clinically as encephalopathy.
The same neuronal injury produces epilepsy, which in the severe early-onset forms is often refractory.
Podocytes are among the cell types that fail under CoQ10 deficiency, and that failure presents as steroid-resistant nephrotic syndrome.
Show evidence (2 references)
"CoQ10 deficiency exerts detrimental effects on the nervous system. Potential consequences are neuronal death, neuroinflammation and cerebral gliosis."
CoQ10 deficiency causes neuronal death, neuroinflammation, and gliosis as downstream tissue injury.
"However, there are many other cellular pathways that also depend on the CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidation)."
Non-bioenergetic CoQ10-dependent pathways (redox homeostasis, ferroptosis defense, sulfide oxidation) are also disrupted.
Pathograph
Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Phenotypes
12Cardiovascular 1
Cardiomyopathy
HP:0001638
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Cardiomyopathy (HP:0001638). HP:0001638 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"cardiomyopathy (5/6)"
Cardiomyopathy was present in 5 of 6 neonatal COQ4 patients.
Ear 1
Sensorineural hearing impairment
HP:0000407
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Sensorineural hearing impairment (HP:0000407). HP:0000407 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype."
COQ6 expression in inner-ear stria vascularis underlies the sensorineural deafness of the oto-renal phenotype.
Eye 1
Optic atrophy
HP:0000648
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Optic atrophy (HP:0000648). HP:0000648 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Here we describe two young sisters with sensorineural deafness followed by optic atrophy, due to a novel homozygous pathogenic variant in PDSS1."
Reports optic atrophy in two sisters with a biallelic PDSS1 variant.
Genitourinary 2
Nephrotic syndrome
HP:0000100
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Steroid-resistant nephrotic syndrome, annotated with Nephrotic syndrome (HP:0000100). HP:0000100 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Each mutation was linked to early-onset SRNS with sensorineural deafness."
Steroid-resistant nephrotic syndrome is a key renal manifestation, shown here for COQ6.
Renal tubular dysfunction
HP:0000124
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Renal tubular dysfunction (HP:0000124). HP:0000124 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"We genotyped a patient with primary coenzyme Q(10) deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction."
Records renal tubular dysfunction in the patient with the biallelic truncating COQ9 variant.
Metabolism 1
Lactic acidosis
Increased circulating lactate concentration
HP:0002151
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Increased circulating lactate concentration (HP:0002151). HP:0002151 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Hyperlactatemia was one of the most common manifestations, accounting for 75% of cases (18/24)."
Hyperlactatemia was among the most common manifestations in neonatal COQ4 disease (18/24).
Musculoskeletal 1
Hypotonia
HP:0001252
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Hypotonia (HP:0001252). HP:0001252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Clinical findings included hypotonia (6/6)"
Hypotonia was present in all six neonatal COQ4 patients in this cohort.
Nervous System 5
Encephalopathy
HP:0001298
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Encephalopathy (HP:0001298). HP:0001298 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Clinical features include encephalopathy, regression, movement disorders, epilepsy and intellectual disability."
Encephalopathy is a recognized core neurologic feature of CoQ10 deficiency.
Seizures
HP:0001250
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Clinical features include encephalopathy, regression, movement disorders, epilepsy and intellectual disability."
Epilepsy/seizures are recognized neurologic features.
Cerebellar atrophy
HP:0001272
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Cerebellar atrophy (HP:0001272). HP:0001272 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"cerebellar atrophy (4/5)"
Cerebellar atrophy was present in 4 of 5 neonatal COQ4 patients with imaging.
Cerebellar ataxia
HP:0001251
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Cerebellar ataxia, annotated with Ataxia (HP:0001251). HP:0001251 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"Here, we report three female siblings of Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, and cognitive disability."
The COQ5 index family's presenting phenotype, reported with a measured CoQ10 deficiency.
Progressive peripheral neuropathy
HP:0007133
Human Phenotype Ontology (HP)
Relation: this clinical feature is this phenotype
This clinical feature is Progressive peripheral neuropathy (HP:0007133). HP:0007133 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
"The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involvement and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay."
Reports progressive neuropathy with lower-limb weakness as the late-onset COQ7 phenotype in a cohort of five new plus nine previously reported patients.
Genetic Associations
10
COQ2
Show evidence (1 reference)
"Transformation of yeast Deltacoq1 and Deltacoq2 strains by mutant yeast COQ1 and mutant human COQ2 genes, respectively, resulted in defective growth on respiratory medium, indicating that these mutations are indeed the cause of OXPHOS deficiency."
Yeast complementation establishes the patients' COQ2 and PDSS1/COQ1 alleles as loss-of-function and as the cause of the OXPHOS defect.
COQ4
Show evidence (2 references)
"We identified five recessive missense mutations in COQ4 segregating with disease in all four families."
Recessive COQ4 missense alleles segregating with disease across four families.
"The early mortality in our cohort suggests that COQ4 is an essential component of the multisubunit complex required for CoQ(10) biosynthesis."
Source for describing COQ4 as a component of the multisubunit biosynthetic complex.
COQ5
Show evidence (1 reference)
"Three variants (1 large tandem duplication, 1 canonical splice-site, 1 missense) that have been reported in 2 probands in 2 publications (PMIDs: 29044765, 37599337) are included in this curation. The mechanism of pathogenicity appears to be loss of function."
ClinGen's summary of the COQ5 allelic evidence and of the loss-of-function mechanism, and the basis for the Moderate grade recorded in the notes.
COQ6
Show evidence (2 references)
"Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping."
Thirteen individuals from seven families carrying biallelic COQ6 variants.
"The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast."
Yeast complementation establishes the patient alleles as loss of function.
COQ8A
Show evidence (1 reference)
"ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q10 (CoQ10) biosynthesis."
Records COQ8A, under its previous symbol ADCK3, as an established participant in CoQ10 biosynthesis.
COQ8B
Show evidence (2 references)
"While various names have been given to the constellation of features seen in those with COQ8B -related disease, pathogenic variants in this gene cause a primary mitochondrial disease."
ClinGen's statement that the COQ8B presentations are one disease entity, which is the lumping decision recorded in the notes.
"Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ10 treatment."
A biallelic COQ8B patient whose renal disease partially remitted on CoQ10, supporting a causative and treatable relationship.
COQ7
Show evidence (2 references)
"Overall, we define two distinct disease presentations of COQ7-related disorder with emerging genotype-phenotype correlation and validate the use of the yeast model for functional studies of COQ7 variants."
The authors' conclusion that COQ7 produces two distinct presentations with a genotype-phenotype correlation.
"We demonstrate that the coenzyme Q analogue 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q levels and rescue the biochemical defect in patient fibroblasts."
Bypassing the COQ7 step in patient fibroblasts restores CoQ, which locates the defect at that enzymatic step.
COQ9
Show evidence (2 references)
"Site-directed mutagenesis targeting the equivalent residue in the yeast Saccharomyces cerevisiae abolished respiratory growth."
Functional confirmation that the truncating COQ9 allele abolishes respiratory competence.
"Cultured skin fibroblasts from the patient had a coenzyme Q(10) biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate."
Patient fibroblasts show a residual CoQ10 biosynthetic rate of 11% of controls together with an accumulated upstream intermediate.
PDSS1
Show evidence (1 reference)
"A genome-wide search for homozygosity in family 1 identified a region of chromosome 10 encompassing the gene prenyldiphosphate synthase, subunit 1 (PDSS1), which encodes the human ortholog of the yeast COQ1 gene, a key enzyme of CoQ10 synthesis."
Maps the first PDSS1 family to chromosome 10 and identifies the gene as the human COQ1 orthologue.
PDSS2
Show evidence (2 references)
"Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts."
Direct enzymatic confirmation that the biallelic PDSS2 variants impair decaprenyl diphosphate synthase activity.
"This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency."
The first reported PDSS2 patient, presented by the authors as evidence of the genetic heterogeneity of primary CoQ10 deficiency.
Medical Actions
2
Coenzyme Q10 supplementation
High-dose oral CoQ10 (ubiquinone/ubiquinol) supplementation is the only disease-directed therapy. Early treatment can reverse or prevent renal disease (around 30 mg/kg/day) and ameliorate neurologic features (up to 70 mg/kg/day); benefit is limited once irreversible organ injury is established, and severe neonatal forms often respond poorly.
Show evidence (2 references)
"We also demonstrate that early diagnosis and treatment of CoQ10 deficiency with oral supplementation (30 mg/kg/d) can reverse renal manifestations and can completely prevent kidney disease over 10 years of follow-up."
Early high-dose oral CoQ10 can reverse and prevent renal disease.
"We show that oral doses of CoQ10 up to 70 mg/kg/d were needed to ameliorate neurologic features."
Higher doses (up to 70 mg/kg/day) were required to ameliorate neurologic features.
Idebenone
Idebenone, a synthetic CoQ10 analogue, was used as an adjunct to control seizures in some patients (10-20 mg/kg/day).
Show evidence (1 reference)
"Additional idebenone was required to control seizures in some cases, and 3 children with neonatal-onset neurologic disease died in early childhood despite receiving high-dose oral CoQ10 from birth."
Idebenone was used as an adjunct to control seizures in some patients.
Biochemical Markers
1
Reduced muscle CoQ10 and respiratory chain activity
Diagnosis
1
Molecular genetic testing
Genome-wide molecular testing (WES/WGS or multigene panels) is the recommended first-line diagnostic approach because there are no pathognomonic blood, muscle, or imaging biomarkers and because early diagnosis enables potentially disease-modifying treatment.
molecular genetic testing
NCIT:C19770
NCI Thesaurus (NCIT)
Results: Detection of biallelic pathogenic variants in a CoQ10 biosynthesis gene confirms the molecular diagnosis and guides treatment.
Show evidence (1 reference)
"An early genome-wide diagnostic approach is needed for expeditious diagnosis of CoQ10 biosynthesis disorder because our study demonstrates that there are no pathognomonic blood, muscle, or imaging biomarkers of these diseases."
Genome-wide molecular testing is recommended because no pathognomonic biomarkers exist.
Progression
1Neonatal/infantile severe multisystem disease
Show evidence (1 reference)
"Additional idebenone was required to control seizures in some cases, and 3 children with neonatal-onset neurologic disease died in early childhood despite receiving high-dose oral CoQ10 from birth."
Neonatal-onset neurologic disease has poor outcomes even with early high-dose CoQ10.
Prevalence
1General population
Primary CoQ10 deficiency is very rare, with prevalence/incidence estimated at less than 1 per 100,000 population.
Related Datasets
1
Survival transcriptome in coenzyme Q deficiency syndrome
geo:GSE33941
Identified by GEO DataSets index search for Primary Coenzyme Q10 Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Animal Models
1
Coq9 knockout Mouse
The Coq9 knockout mouse recapitulates encephalopathy with cerebral gliosis and spongiosis, modeling the neurologic injury of CoQ10 deficiency.
Species
Mouse
Genotype
Coq9 knockout
Show evidence (1 reference)
"CoQ10 deficiency exerts detrimental effects on the nervous system. Potential consequences are neuronal death, neuroinflammation and cerebral gliosis."
Model and human evidence converge on neuronal death, neuroinflammation, and cerebral gliosis as consequences of CoQ10 deficiency.
Source YAML
click to showname: Primary Coenzyme Q10 Deficiency
creation_date: "2026-06-17T00:00:00Z"
category: Metabolic Disorder
parents:
- Mendelian Disorder
- Metabolic Disorder
- Mitochondrial Disorder
disease_term:
preferred_term: primary coenzyme Q10 deficiency
term:
id: MONDO:0018151
label: coenzyme Q10 deficiency
description: >-
Primary coenzyme Q10 (CoQ10, ubiquinone) deficiency is a clinically and
genetically heterogeneous group of autosomal recessive mitochondrial
disorders caused by biallelic pathogenic variants in nuclear genes required
for endogenous CoQ10 biosynthesis. Reduced tissue CoQ10 impairs electron
transfer through the mitochondrial respiratory chain (between complexes I/II
and complex III), compromises oxidative phosphorylation, and disrupts
additional CoQ-dependent processes (antioxidant defense, pyrimidine and
sulfide metabolism, ferroptosis protection), producing multisystem,
high-energy-organ disease. Phenotypes range from lethal neonatal
encephalomyopathy to childhood/adult-onset cerebellar ataxia, with prominent
renal (steroid-resistant nephrotic syndrome), neurologic, cardiac, and
sensorineural manifestations that vary by causal gene. It is one of the few
potentially treatable mitochondrial disorders: high-dose oral CoQ10
supplementation can reverse or prevent renal disease and ameliorate
neurologic features if given before irreversible organ injury.
synonyms:
- primary CoQ10 deficiency
- primary ubiquinone deficiency
- coenzyme Q10 biosynthesis deficiency
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:37627647
reference_title: "Primary Coenzyme Q10 Deficiency: An Update."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Primary CoQ10 deficiency results from mutations in genes involved in the
CoQ10 biosynthetic pathway.
explanation: >-
Primary CoQ10 deficiency is caused by biallelic pathogenic variants in
CoQ10 biosynthesis genes, inherited in an autosomal recessive pattern.
classifications:
harrisons_chapter:
- classification_value: GENETICS_ENVIRONMENT_DISEASE
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The CoQ10 biosynthesis pathway consists of several enzymes, which are
encoded by the nuclear DNA.
explanation: >-
Primary CoQ10 deficiency is a Mendelian (autosomal recessive) inborn
error of CoQ10 biosynthesis, placing it in Harrison's Genetics Part.
- classification_value: ENDOCRINOLOGY_METABOLISM
evidence:
- reference: PMID:37508007
reference_title: "Biosynthesis, Deficiency, and Supplementation of Coenzyme Q."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cells rely on endogenous CoQ biosynthesis, and defects in this
still-not-completely understood pathway result in primary CoQ
deficiencies, a group of conditions biochemically characterised by
decreased tissue CoQ levels, which in turn are linked to functional
defects.
explanation: >-
Primary CoQ10 deficiency is an inborn error of metabolism (a defect of
the CoQ10 biosynthetic pathway), placing it in Harrison's
Endocrinology/Metabolism Part.
mechanistic_category:
- classification_value: mitochondrial disease
evidence:
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Disorders of coenzyme Q10 (CoQ10) biosynthesis comprise a group of 11
clinically and genetically heterogeneous rare primary mitochondrial
diseases.
explanation: >-
Primary CoQ10 deficiency disorders are classified as primary
mitochondrial diseases.
has_subtypes:
- name: COQ2
display_name: COQ2-related (CoQ10 deficiency-1)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 1
term:
id: MONDO:0011829
label: coenzyme Q10 deficiency, primary, 1
description: >-
COQ2 (4-hydroxybenzoate polyprenyltransferase) was the first CoQ10
biosynthesis gene linked to disease. The phenotype spans infantile
multisystem encephalomyopathy with nephrotic syndrome to isolated
steroid-resistant nephropathy. This form is curated in full as its own
dismech entry, COQ2-Related_Primary_Coenzyme_Q10_Deficiency, and is
cross-referenced here rather than duplicated.
genes:
- preferred_term: COQ2
term:
id: hgnc:25223
label: COQ2
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:17186472
reference_title: "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
quote_role: BACKGROUND
snippet: >-
The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a
child with encephalomyopathy and nephrotic syndrome and in a younger
sibling with only nephropathy.
explanation: >-
COQ2 was the first identified primary CoQ10 biosynthesis gene, causing
encephalomyopathy with nephrotic syndrome. The quoted sentence is this
PDSS2 report's summary of the earlier COQ2 patients rather than its own
result.
- reference: PMID:17332895
reference_title: "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the second family, direct sequencing of OH-benzoate polyprenyltransferase
(COQ2), the human ortholog of the yeast COQ2 gene, identified a single base
pair frameshift deletion resulting in a premature stop codon (c.1198delT,
N401fsX415).
explanation: >-
An independent family with a biallelic truncating COQ2 variant, naming the
enzyme activity COQ2 contributes to the pathway.
- name: COQ4
display_name: COQ4-related (lethal neonatal encephalomyopathy)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 7
term:
id: MONDO:0014562
label: neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome
description: >-
COQ4 variants cause an autosomal recessive lethal neonatal mitochondrial
encephalomyopathy with hypotonia, encephalopathy, seizures, cerebellar
atrophy, cardiomyopathy, and lactic acidosis; a founder mutation occurs in
the Ashkenazi Jewish population, and a high incidence is reported in
southern China. This form is curated in full as its own dismech entry,
COQ4-Related_Neonatal_Encephalomyopathy, and is cross-referenced here
rather than duplicated.
genes:
- preferred_term: COQ4
term:
id: hgnc:19693
label: COQ4
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Mutations in COQ4 cause an autosomal recessive lethal neonatal
mitochondrial encephalomyopathy associated with a founder mutation in the
Ashkenazi Jewish population.
explanation: >-
COQ4 variants produce a severe lethal neonatal encephalomyopathy form of
primary CoQ10 deficiency.
- name: COQ5
display_name: COQ5-related (CoQ10 deficiency-9)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 9
term:
id: MONDO:0033615
label: coenzyme q10 deficiency, primary, 9
description: >-
COQ5 encodes a methyltransferase of the CoQ10 biosynthetic pathway. Biallelic
COQ5 variants were reported in three siblings with cerebellar ataxia,
encephalopathy, generalized tonic-clonic seizures and cognitive disability,
whose blood and muscle CoQ10 were reduced and who improved on CoQ10
supplementation. ClinGen grades the gene-to-mitochondrial-disease relationship
Moderate rather than Definitive, on two probands.
genes:
- preferred_term: COQ5
term:
id: hgnc:28722
label: COQ5
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:29044765
reference_title: "A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Whole-exome and subsequent whole-genome sequencing identified biallelic
duplications in the COQ5 gene, leading to reduced levels of CoQ10 in
peripheral white blood cells of all affected individuals and reduced CoQ10
levels in the only muscle tissue available from one affected proband.
explanation: >-
Establishes biallelic COQ5 variants as a cause of measured CoQ10
deficiency in patients.
- reference: PMID:29044765
reference_title: "A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is the first report of primary CoQ10 deficiency caused by loss of
function of COQ5, with delineation of the clinical, laboratory,
histological, and molecular features, and insights regarding targeted
treatment with CoQ10 supplementation.
explanation: >-
The authors classify the COQ5 phenotype as primary CoQ10 deficiency and
state the mechanism as loss of function.
- reference: PMID:29044765
reference_title: "A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CoQ10 supplementation led to clinical improvement and increased the
concentrations of CoQ10 in blood.
explanation: >-
Source for the treatment response recorded in this subtype description.
- reference: CGGV:assertion_9b9c2846-d034-46f4-87ba-525bed7efe9c-2024-07-10T160000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: "COQ5 | HGNC:28722 | mitochondrial disease | MONDO:0044970 | AR | Moderate | SOP10 | Cerebellar Ataxia Gene Curation Expert Panel"
explanation: >-
ClinGen's Cerebellar Ataxia expert panel grades COQ5 Moderate for
autosomal recessive mitochondrial disease, which is the citable
gene-validity basis for giving COQ5 its own subtype row.
- name: COQ6
display_name: COQ6-related (SRNS with sensorineural deafness)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 6
term:
id: MONDO:0013836
label: familial steroid-resistant nephrotic syndrome with sensorineural deafness
description: >-
COQ6 (CoQ10 biosynthesis monooxygenase 6) mutations produce early-onset
steroid-resistant nephrotic syndrome with sensorineural deafness, an
oto-renal phenotype reflecting COQ6 expression in podocytes and inner-ear
stria vascularis. This form is curated in full as its own dismech entry,
COQ6-Related_Steroid-Resistant_Nephrotic_Syndrome, and is cross-referenced
here rather than duplicated.
genes:
- preferred_term: COQ6
term:
id: hgnc:20233
label: COQ6
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:21540551
reference_title: "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Each mutation was linked to early-onset SRNS with sensorineural deafness.
explanation: >-
COQ6 mutations cause steroid-resistant nephrotic syndrome with
sensorineural deafness.
- name: COQ8A
display_name: COQ8A/ADCK3-related (cerebellar ataxia)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 4
term:
id: MONDO:0012784
label: autosomal recessive ataxia due to ubiquinone deficiency
description: >-
The COQ8A (ADCK3) cerebellar-ataxia form (primary CoQ10 deficiency-4,
ARCA2/SCAR9) is curated as a separate dismech entry
(Autosomal_Recessive_Ataxia_Due_to_Ubiquinone_Deficiency). It is
cross-referenced here as an already-split member and is not duplicated in
this umbrella entry.
genes:
- preferred_term: COQ8A
term:
id: hgnc:16812
label: COQ8A
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thus far, 11 disease genes are known (PDSS1, PDSS2, COQ2, COQ4,
COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9 and HPDL).
explanation: >-
COQ8A is one of the recognized primary CoQ10 biosynthesis disease genes;
its cerebellar-ataxia form is curated in a dedicated dismech entry.
- name: COQ8B
display_name: COQ8B/ADCK4-related (SRNS)
subtype_term:
preferred_term: COQ8B nephrotic syndrome
term:
id: MONDO:0014257
label: nephrotic syndrome, type 9
description: >-
COQ8B (ADCK4) mutations cause steroid-resistant nephrotic syndrome,
typically with later (childhood/adolescent) onset than COQ6, and may be
partially responsive to CoQ10 supplementation. MONDO files this form under
familial idiopathic steroid-resistant nephrotic syndrome as nephrotic
syndrome type 9, not beneath the coenzyme Q10 deficiency umbrella, so the
subtype term here is the renal-nosology class rather than a numbered CoQ10
deficiency class.
genes:
- preferred_term: COQ8B
term:
id: hgnc:19041
label: COQ8B
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here, using a combination of homozygosity mapping and whole human exome
resequencing, we identified mutations in the aarF domain containing
kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated
families.
explanation: >-
COQ8B/ADCK4 mutations cause steroid-resistant nephrotic syndrome through
disrupted CoQ10 biosynthesis.
- reference: CGGV:assertion_43b1c614-38c9-4729-8661-eecc0d24a364-2023-02-06T050000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: "COQ8B | HGNC:19041 | mitochondrial disease | MONDO:0044970 | AR | Definitive | SOP9 | Mitochondrial Diseases Gene Curation Expert Panel"
explanation: >-
ClinGen grades COQ8B Definitive for autosomal recessive mitochondrial
disease, and lumps the COQ8B renal and mitochondrial presentations into
one disease entity.
- name: COQ7
display_name: COQ7-related (CoQ10 deficiency-8)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 8
term:
id: MONDO:0014754
label: primary coenzyme Q10 deficiency 8
description: >-
COQ7 encodes the mitochondrial demethoxyubiquinone hydroxylase of the CoQ10
biosynthetic pathway. Two clinical
presentations are described: a neonatal-onset form with severe
neuromuscular, cardiorespiratory and renal involvement, and a late-onset
form with progressive neuropathy and lower-limb weakness. MONDO places the
COQ7 distal hereditary motor neuronopathy class MONDO:0957874 beneath this
numbered form; that late-onset neuropathy is treated in dismech as a
differential_diagnoses row on Distal_Hereditary_Motor_Neuronopathy_Type_9
rather than as a separate entry.
genes:
- preferred_term: COQ7
term:
id: hgnc:2244
label: COQ7
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:26084283
reference_title: "Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report the first patient with primary coenzyme Q deficiency due to a
homozygous COQ7 mutation and a potentially beneficial treatment using
2,4DHB.
explanation: >-
The first reported patient with primary CoQ deficiency caused by a
biallelic COQ7 variant.
- reference: PMID:37392700
reference_title: "Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ(10) deficiency: Hypomorphic variants and two distinct disease entities."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The main clinical features included a neonatal-onset presentation with
severe neuromuscular, cardiorespiratory and renal involvement and a
late-onset disease presenting with progressive neuropathy, lower extremity
weakness, abnormal gait, and variable developmental delay.
explanation: >-
Delineates the two COQ7 clinical presentations recorded in this subtype
description.
- name: COQ9
display_name: COQ9-related (neonatal encephalomyopathy)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 5
term:
id: MONDO:0013840
label: encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome
description: >-
COQ9 deficiency causes a severe neonatal-onset encephalomyopathy; the Coq9
knockout mouse recapitulates encephalopathy with cerebral gliosis and
spongiosis. The index patient presented with neonatal lactic acidosis and
went on to develop intractable seizures, global developmental delay,
hypertrophic cardiomyopathy and renal tubular dysfunction, which are the
features MONDO's label for this numbered form names.
genes:
- preferred_term: COQ9
term:
id: hgnc:25302
label: COQ9
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:19375058
reference_title: "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sequence analysis demonstrated a homozygous stop mutation affecting a
highly conserved residue of COQ9, leading to the truncation of 75 amino
acids.
explanation: >-
Identifies the biallelic truncating COQ9 variant in the index patient with
primary CoQ10 deficiency.
- reference: PMID:19375058
reference_title: "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We genotyped a patient with primary coenzyme Q(10) deficiency who
presented with neonatal lactic acidosis and later developed multisytem
disease including intractable seizures, global developmental delay,
hypertrophic cardiomyopathy, and renal tubular dysfunction.
explanation: >-
Source for the clinical course recorded in this subtype description.
- reference: CGGV:assertion_5bd50af5-d882-49e1-afd5-d68f253055d7-2024-01-29T170000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: "COQ9 | HGNC:25302 | mitochondrial disease | MONDO:0044970 | AR | Definitive | SOP10 | Mitochondrial Diseases Gene Curation Expert Panel"
explanation: >-
ClinGen grades COQ9 Definitive for autosomal recessive mitochondrial
disease.
- name: PDSS1
display_name: PDSS1-related (CoQ10 deficiency-2)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 2
term:
id: MONDO:0013837
label: deafness-encephaloneuropathy-obesity-valvulopathy syndrome
description: >-
PDSS1 encodes a subunit of decaprenyl diphosphate synthase, the first
enzyme of the CoQ10 biosynthetic pathway responsible for assembly of the
polyisoprenoid side chain. MONDO's label for this numbered form names an
encephaloneuropathy with deafness, obesity and valvulopathy; the family cited
below presented with sensorineural deafness followed by optic atrophy.
genes:
- preferred_term: PDSS1
term:
id: hgnc:17759
label: PDSS1
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:17332895
reference_title: "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sequencing of PDSS1 identified a homozygous nucleotide substitution
modifying a conserved amino acid of the protein (D308E).
explanation: >-
The first reported biallelic PDSS1 variant in a family with CoQ10
deficiency.
- reference: PMID:33285023
reference_title: Missense PDSS1 mutations in CoenzymeQ10 synthesis cause optic atrophy and sensorineural deafness.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we describe two young sisters with sensorineural deafness followed by
optic atrophy, due to a novel homozygous pathogenic variant in PDSS1.
explanation: >-
An independent PDSS1 family, and the source for the sensory presentation
recorded in this subtype description.
- reference: CGGV:assertion_afd9c803-3a72-443a-9ab7-dcb048aa5c6c-2023-07-31T040000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: "PDSS1 | HGNC:17759 | mitochondrial disease | MONDO:0044970 | AR | Moderate | SOP10 | Mitochondrial Diseases Gene Curation Expert Panel"
explanation: >-
ClinGen grades PDSS1 Moderate rather than Definitive for autosomal
recessive mitochondrial disease.
- name: PDSS2
display_name: PDSS2-related (Leigh syndrome with nephropathy)
subtype_term:
preferred_term: coenzyme Q10 deficiency, primary, 3
term:
id: MONDO:0013838
label: coenzyme Q10 deficiency, primary, 3
description: >-
PDSS2 encodes a subunit of decaprenyl diphosphate synthase, the first
enzyme of CoQ10 biosynthesis. Pathogenic variants cause severe Leigh
syndrome with nephrotic syndrome and CoQ10 deficiency in muscle and
fibroblasts.
genes:
- preferred_term: PDSS2
term:
id: hgnc:23041
label: PDSS2
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:17186472
reference_title: "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here, we describe an infant with severe Leigh syndrome, nephrotic
syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound
heterozygous mutations in the PDSS2 gene, which encodes a subunit of
decaprenyl diphosphate synthase, the first enzyme of the CoQ(10)
biosynthetic pathway.
explanation: >-
PDSS2 mutations cause Leigh syndrome with nephropathy and CoQ10
deficiency.
- reference: CGGV:assertion_5e0928f3-2b7d-4622-bc96-68a4d0078826-2021-03-11T172336.036Z
supports: SUPPORT
evidence_source: OTHER
snippet: "PDSS2 | HGNC:23041 | Leigh syndrome | MONDO:0009723 | AR | Moderate | SOP7 | Mitochondrial Diseases Gene Curation Expert Panel"
explanation: >-
ClinGen grades PDSS2 Moderate, and records the gene against Leigh
syndrome rather than against a numbered CoQ10 deficiency class.
pathophysiology:
- name: Defective Polyisoprenoid Side-Chain Assembly and Attachment
description: >-
The first steps of CoQ10 biosynthesis build the polyisoprenoid tail and
attach it to the 4-hydroxybenzoate ring. Only three of the disease genes act
here: PDSS1 and PDSS2 each encode a subunit of the decaprenyl diphosphate
synthase that supplies the side chain, and COQ2 is the polyprenyltransferase
that joins it to the ring. Biallelic defects in this segment therefore block CoQ10 assembly at its
earliest committed step, and the reported phenotypes of this segment include
prominent visual involvement.
biological_scale: MOLECULAR
genes:
- preferred_term: PDSS1
term:
id: hgnc:17759
label: PDSS1
- preferred_term: PDSS2
term:
id: hgnc:23041
label: PDSS2
- preferred_term: COQ2
term:
id: hgnc:25223
label: COQ2
molecular_functions:
- preferred_term: decaprenyl diphosphate synthase activity
term:
id: GO:0097269
label: all-trans-decaprenyl-diphosphate synthase activity
modifier: DECREASED
- preferred_term: 4-hydroxybenzoate polyprenyltransferase activity
term:
id: GO:0008412
label: 4-hydroxybenzoate polyprenyltransferase activity
modifier: DECREASED
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: OTHER
quote_role: REVIEW_SYNTHESIS
snippet: >-
Only three enzymes (PDSS1, PDSS2 and COQ2) are required for assembly and
attachment of the polyisoprenoid side chain.
explanation: >-
Defines the three genes that act at this segment of the pathway, which is
the gene set bound on this node.
- reference: CGGV:assertion_afd9c803-3a72-443a-9ab7-dcb048aa5c6c-2023-07-31T040000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The PDSS1 gene encodes prenyl diphosphate synthase subunit 1, an enzyme
that supplies decaprenyl diphosphate, the precursor for the side chain of
the isoprenoid quinone Coenzyme Q10 that functions as a mobile electron
carrier in the respiratory chain, as well as other mitochondrial functions
including antioxidant properties.
explanation: >-
Names the decaprenyl diphosphate synthase activity bound on this node and
its role in supplying the CoQ10 side chain.
- reference: PMID:17332895
reference_title: "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the second family, direct sequencing of OH-benzoate polyprenyltransferase
(COQ2), the human ortholog of the yeast COQ2 gene, identified a single base
pair frameshift deletion resulting in a premature stop codon (c.1198delT,
N401fsX415).
explanation: >-
Names the 4-hydroxybenzoate polyprenyltransferase activity bound on this
node, and the biallelic COQ2 defect that abolishes it.
- reference: PMID:33285023
reference_title: Missense PDSS1 mutations in CoenzymeQ10 synthesis cause optic atrophy and sensorineural deafness.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The visual system seems to be mainly involved when the first steps of
CoQ10 synthesis are impaired (PDSS1, PDSS2, and COQ2 deficiency).
explanation: >-
Groups PDSS1, PDSS2 and COQ2 as the first-step enzymes and reports the
phenotypic emphasis this node's description records.
downstream:
- target: Defective CoQ10 Biosynthesis
description: >-
Failure to assemble or attach the polyisoprenoid side chain blocks CoQ10
production at the earliest committed step.
causal_link_type: DIRECT
- name: Defective Benzoquinone Head-Group Modification
description: >-
Most of the CoQ10 biosynthesis enzymes act after side-chain attachment, on
the benzoquinone ring, and may assemble into resolvable domains described as
COQ complexes. COQ4, COQ5, COQ6, COQ7 and COQ9 act in this segment: COQ4 is
the zinc-dependent C1 decarboxylase, COQ5 the pathway's C-methyltransferase,
COQ6 its flavin-dependent ring monooxygenase, COQ7 the NADH-dependent
demethoxyubiquinone hydroxylase, and COQ9 a lipid-binding protein that
presents its bound lipid to COQ7. Biallelic defects in this segment therefore
block CoQ10 maturation after the side chain has been attached.
biological_scale: MOLECULAR
genes:
- preferred_term: COQ4
term:
id: hgnc:19693
label: COQ4
- preferred_term: COQ5
term:
id: hgnc:28722
label: COQ5
- preferred_term: COQ6
term:
id: hgnc:20233
label: COQ6
- preferred_term: COQ7
term:
id: hgnc:2244
label: COQ7
- preferred_term: COQ9
term:
id: hgnc:25302
label: COQ9
molecular_functions:
- preferred_term: COQ4 C1 decarboxylase activity
term:
id: GO:0120539
label: 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase activity
modifier: DECREASED
- preferred_term: COQ6 C5 ring hydroxylase activity
term:
id: GO:0106364
label: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity
modifier: DECREASED
- preferred_term: COQ5 C2 ring methyltransferase activity
term:
id: GO:0008425
label: 2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity
modifier: DECREASED
- preferred_term: COQ7 NADH-dependent demethoxyubiquinone hydroxylase activity
term:
id: GO:0160224
label: 3-demethoxyubiquinone 3-hydroxylase (NADH) activity
modifier: DECREASED
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: OTHER
quote_role: REVIEW_SYNTHESIS
snippet: >-
The majority of these enzymes are responsible for modifications of the
CoQ-head group (benzoquinone ring).
explanation: >-
Establishes head-group modification as the segment most of the CoQ10
biosynthesis enzymes act in.
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: OTHER
quote_role: REVIEW_SYNTHESIS
snippet: >-
The head-modifying enzymes may assemble into resolvable domains,
representing COQ complexes.
explanation: >-
Source for describing this segment's enzymes as assembling into COQ
complexes.
- reference: PMID:37392700
reference_title: "Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ(10) deficiency: Hypomorphic variants and two distinct disease entities."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Biallelic pathogenic variants in COQ7, encoding mitochondrial
5-demethoxyubiquinone hydroxylase, have been reported in nine patients
from seven families.
explanation: >-
Names the demethoxyubiquinone hydroxylase activity bound on this node and
the gene that carries it.
- reference: CGGV:assertion_9b9c2846-d034-46f4-87ba-525bed7efe9c-2024-07-10T160000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The COQ5 gene encodes coenzyme Q5, methyltransferase which is involved in
mitochondrial ubiquinone (coenzyme Q10, CoQ10) biosynthesis.
explanation: Places COQ5's methyltransferase activity in this segment.
- reference: PMID:25339443
reference_title: Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The conserved COQ9 residues necessary for its interaction with COQ7
comprise a surface patch around the lipid-binding site, suggesting that
COQ9 might serve to present its bound lipid to COQ7.
explanation: >-
Structural and mass-spectrometry work placing COQ9 as COQ7's lipid-binding
partner within this segment.
- reference: PMID:38295803
reference_title: COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
We demonstrate that COQ4 complements an Escherichia coli strain deficient
for C1 decarboxylation and hydroxylation and that COQ4 displays oxidative
decarboxylation activity in the non-CoQ producer Corynebacterium
glutamicum.
explanation: >-
Establishes COQ4 as the C1 decarboxylase of the head-group pathway, the
activity bound on this node for COQ4.
- reference: PMID:38425362
reference_title: In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
COQ6, a class A flavin-dependent monooxygenase, represents the first
protein in the CoQ head group biosynthetic pathway and performs C5
hydroxylation converting 1 to 2
explanation: >-
Reconstitution with resurrected ancestral animal COQ enzymes assigns the
C5 ring hydroxylation bound on this node to COQ6.
- reference: PMID:38425362
reference_title: In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
COQ5 was incubated overnight at 30 °C with SAM and its substrate, 4b;
GC/MS analysis confirmed enzymatic activity and production of 5
explanation: >-
Demonstrates the SAM-dependent C2 ring methylation by COQ5 bound on this
node.
- reference: PMID:38425362
reference_title: In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis.
supports: SUPPORT
evidence_source: IN_VITRO
quote_role: BACKGROUND
snippet: >-
COQ7 is an NADH-dependent hydroxylase that possesses a carboxylate-bridged
diiron centre and converts 5 to 6
explanation: >-
Identifies COQ7's hydroxylation as NADH-dependent, which is why the
NADH-specific demethoxyubiquinone hydroxylase term is bound for COQ7.
downstream:
- target: Defective CoQ10 Biosynthesis
description: >-
Failure to complete benzoquinone ring modification leaves CoQ10 unfinished
and reduces mature CoQ10.
causal_link_type: DIRECT
- name: Defective COQ8 Kinase Support of CoQ10 Biosynthesis
description: >-
COQ8A and COQ8B are closely similar atypical kinases that support the CoQ10
biosynthetic machinery rather than being assigned a named chemical step of the
pathway. COQ8B localises to the mitochondrial matrix of kidney podocytes and
interacts with pathway members including COQ6 and COQ7, and COQ8A was
established as a pathway participant before COQ8B was identified. Loss of
COQ8B reduces cellular CoQ10 in patient-derived cells.
biological_scale: MOLECULAR
genes:
- preferred_term: COQ8A
term:
id: hgnc:16812
label: COQ8A
- preferred_term: COQ8B
term:
id: hgnc:19041
label: COQ8B
molecular_functions:
- preferred_term: COQ8 ATPase activity
term:
id: GO:0016887
label: ATP hydrolysis activity
modifier: DECREASED
cell_types:
- preferred_term: podocyte
term:
id: CL:0000653
label: podocyte
evidence:
- reference: PMID:27499294
reference_title: Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Although COQ8 was predicted to be a protein kinase, we demonstrate that it
lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase
activity and interacts with lipid CoQ intermediates
explanation: >-
Biochemistry of COQ8A and its yeast orthologue Coq8p shows ATPase activity
rather than canonical protein kinase activity, which is why the node binds
ATP hydrolysis activity rather than a protein kinase term.
- reference: PMID:27499294
reference_title: Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Interspecies biochemical analyses show that COQ8A and yeast Coq8p
specifically stabilize a CoQ biosynthesis complex through unorthodox PKL
functions.
explanation: >-
Places COQ8A's support role at the level of the CoQ biosynthesis complex,
as the node description states.
- reference: CGGV:assertion_43b1c614-38c9-4729-8661-eecc0d24a364-2023-02-06T050000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The COQ8B gene encodes the COQ8B protein, which is an atypical kinase that
is expressed in the podocytes of the kidney and localizes to the
mitochondrial matrix, where it participates in coenzyme Q10 synthesis.
explanation: >-
Source for describing COQ8B as an atypical kinase participating in CoQ10
synthesis, and for the podocyte cell type bound on this node.
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
In human podocytes, ADCK4 interacted with members of the CoQ10
biosynthesis pathway, including COQ6, which has been linked with SRNS and
COQ7.
explanation: >-
Shows COQ8B, then named ADCK4, physically associating with head-group
enzymes of the pathway in human podocytes.
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: >-
ADCK4 was highly similar to ADCK3, which has been shown to participate in
coenzyme Q10 (CoQ10) biosynthesis.
explanation: >-
Records COQ8A, then named ADCK3, as an already established participant in
CoQ10 biosynthesis, and as the paralogue by whose similarity COQ8B was
recognised.
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Mutations in ADCK4 resulted in reduced CoQ10 levels and reduced
mitochondrial respiratory enzyme activity in cells isolated from
individuals with SRNS and transformed lymphoblasts.
explanation: >-
Patient-derived cells carrying biallelic COQ8B variants show the reduced
CoQ10 this node's defect produces.
downstream:
- target: Defective CoQ10 Biosynthesis
description: >-
Loss of COQ8 kinase support of the biosynthetic machinery reduces cellular
CoQ10.
causal_link_type: DIRECT
- name: Defective CoQ10 Biosynthesis
description: >-
Biallelic pathogenic variants in any of the nuclear CoQ10 biosynthesis
genes (PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9)
reduce endogenous CoQ10 production, lowering tissue and cellular CoQ10
levels. This is the shared upstream lesion across all primary CoQ10
deficiency subtypes.
genes:
- preferred_term: PDSS1
term:
id: hgnc:17759
label: PDSS1
- preferred_term: PDSS2
term:
id: hgnc:23041
label: PDSS2
- preferred_term: COQ2
term:
id: hgnc:25223
label: COQ2
- preferred_term: COQ4
term:
id: hgnc:19693
label: COQ4
- preferred_term: COQ5
term:
id: hgnc:28722
label: COQ5
- preferred_term: COQ6
term:
id: hgnc:20233
label: COQ6
- preferred_term: COQ7
term:
id: hgnc:2244
label: COQ7
- preferred_term: COQ8A
term:
id: hgnc:16812
label: COQ8A
- preferred_term: COQ8B
term:
id: hgnc:19041
label: COQ8B
- preferred_term: COQ9
term:
id: hgnc:25302
label: COQ9
biological_processes:
- preferred_term: ubiquinone biosynthetic process
term:
id: GO:0006744
label: ubiquinone biosynthetic process
modifier: DECREASED
chemical_entities:
- preferred_term: coenzyme Q10
term:
id: CHEBI:46245
label: coenzyme Q10
modifier: DECREASED
evidence:
- reference: PMID:37627647
reference_title: "Primary Coenzyme Q10 Deficiency: An Update."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In man, at least 10 genes are required for the biosynthesis of functional
CoQ10, a mutation in any one of which can result in a deficit in CoQ10
status.
explanation: >-
Defects in any of the CoQ10 biosynthesis genes reduce functional CoQ10,
the shared upstream defect.
downstream:
- target: Impaired Respiratory Chain Electron Transport
description: Reduced CoQ10 impairs electron transfer in the respiratory chain.
causal_link_type: DIRECT
- name: Impaired Respiratory Chain Electron Transport
description: >-
CoQ10 normally shuttles electrons from respiratory chain complexes I and II
to complex III. Reduced CoQ10 impairs this electron transfer, decreasing
oxidative phosphorylation and ATP synthesis, biochemically detectable as
reduced combined complex I+III and II+III activities.
biological_processes:
- preferred_term: respiratory electron transport chain
term:
id: GO:0022904
label: respiratory electron transport chain
modifier: DECREASED
- preferred_term: oxidative phosphorylation
term:
id: GO:0006119
label: oxidative phosphorylation
modifier: DECREASED
evidence:
- reference: PMID:17186472
reference_title: "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers
electrons from mitochondrial respiratory chain complexes I and II to
complex III.
explanation: >-
CoQ10 transfers electrons from complexes I and II to complex III; its
deficiency impairs respiratory electron transport.
downstream:
- target: Loss of Antioxidant Defense and Multisystem Energy Failure
description: >-
Energy failure combined with loss of CoQ10 antioxidant and redox
functions drives multisystem injury.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Loss of Antioxidant Defense and Multisystem Energy Failure
description: >-
Beyond bioenergetics, CoQ10 is a lipid-soluble antioxidant and supports
redox homeostasis, ferroptosis defense, and sulfide oxidation. Combined
energy failure and loss of antioxidant/redox protection produce multisystem
injury, with the nervous system, kidney, heart, and sensory organs
particularly vulnerable. Neurologic injury involves neuronal death,
neuroinflammation, and cerebral gliosis.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
- preferred_term: podocyte
term:
id: CL:0000653
label: podocyte
biological_processes:
- preferred_term: response to oxidative stress
term:
id: GO:0006979
label: response to oxidative stress
modifier: INCREASED
- preferred_term: ferroptosis
term:
id: GO:0097707
label: ferroptosis
modifier: INCREASED
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CoQ10 deficiency exerts detrimental effects on the nervous system.
Potential consequences are neuronal death, neuroinflammation and cerebral
gliosis.
explanation: >-
CoQ10 deficiency causes neuronal death, neuroinflammation, and gliosis as
downstream tissue injury.
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
However, there are many other cellular pathways that also depend on the
CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidation).
explanation: >-
Non-bioenergetic CoQ10-dependent pathways (redox homeostasis, ferroptosis
defense, sulfide oxidation) are also disrupted.
downstream:
- target: Encephalopathy
description: >-
Neuronal death, neuroinflammation and gliosis in the CoQ10-deficient
nervous system present clinically as encephalopathy.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features include encephalopathy, regression, movement disorders,
epilepsy and intellectual disability.
explanation: >-
Names encephalopathy as a clinical consequence of the nervous-system
injury this node describes.
- target: Seizures
description: >-
The same neuronal injury produces epilepsy, which in the severe
early-onset forms is often refractory.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features include encephalopathy, regression, movement disorders,
epilepsy and intellectual disability.
explanation: >-
Names epilepsy as a clinical consequence of the nervous-system injury
this node describes.
- target: Nephrotic syndrome
description: >-
Podocytes are among the cell types that fail under CoQ10 deficiency, and
that failure presents as steroid-resistant nephrotic syndrome.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic
syndrome-associated phenotypes.
explanation: >-
Loss of a CoQ10 biosynthesis gene reproduces nephrotic syndrome in two
animal models, supporting the mechanism-to-phenotype step.
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
directness: INDIRECT
evidence_source: HUMAN_CLINICAL
snippet: >-
We also demonstrate that early diagnosis and treatment of CoQ10
deficiency with oral supplementation (30 mg/kg/d) can reverse renal
manifestations and can completely prevent kidney disease over 10 years of
follow-up.
explanation: >-
Restoring CoQ10 reverses and prevents the renal disease in patients,
which supports the edge by therapeutic response rather than by direct
observation of the intervening steps.
phenotypes:
- category: Phenotypic abnormality
name: Encephalopathy
description: >-
Encephalopathy with developmental delay/regression is a core neurologic
manifestation, especially in neonatal/infantile-onset forms.
phenotype_term:
preferred_term: Encephalopathy
term:
id: HP:0001298
label: Encephalopathy
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features include encephalopathy, regression, movement disorders,
epilepsy and intellectual disability.
explanation: >-
Encephalopathy is a recognized core neurologic feature of CoQ10
deficiency.
- category: Phenotypic abnormality
name: Seizures
description: Epilepsy/seizures are common, particularly in severe early-onset forms.
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features include encephalopathy, regression, movement disorders,
epilepsy and intellectual disability.
explanation: Epilepsy/seizures are recognized neurologic features.
- category: Phenotypic abnormality
name: Hypotonia
subtype: COQ4
description: Hypotonia is a frequent feature of neonatal-onset COQ4 disease.
phenotype_term:
preferred_term: Hypotonia
term:
id: HP:0001252
label: Hypotonia
evidence:
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Clinical findings included hypotonia (6/6)"
explanation: >-
Hypotonia was present in all six neonatal COQ4 patients in this cohort.
- category: Phenotypic abnormality
name: Cerebellar atrophy
description: >-
Cerebellar atrophy is a characteristic neuroimaging finding, prominent in
COQ8A ataxia and seen in neonatal COQ4 disease.
phenotype_term:
preferred_term: Cerebellar atrophy
term:
id: HP:0001272
label: Cerebellar atrophy
evidence:
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "cerebellar atrophy (4/5)"
explanation: >-
Cerebellar atrophy was present in 4 of 5 neonatal COQ4 patients with
imaging.
- category: Phenotypic abnormality
name: Nephrotic syndrome
description: >-
Steroid-resistant nephrotic syndrome is a major renal manifestation in
COQ2, COQ6, and COQ8B forms and can progress to end-stage kidney disease.
phenotype_term:
preferred_term: Steroid-resistant nephrotic syndrome
term:
id: HP:0000100
label: Nephrotic syndrome
evidence:
- reference: PMID:21540551
reference_title: "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Each mutation was linked to early-onset SRNS with sensorineural deafness.
explanation: >-
Steroid-resistant nephrotic syndrome is a key renal manifestation, shown
here for COQ6.
- category: Phenotypic abnormality
name: Sensorineural hearing impairment
description: >-
Sensorineural deafness accompanies nephrotic syndrome in the COQ6 oto-renal
form, reflecting COQ6 expression in inner-ear stria vascularis cells.
phenotype_term:
preferred_term: Sensorineural hearing impairment
term:
id: HP:0000407
label: Sensorineural hearing impairment
evidence:
- reference: PMID:21540551
reference_title: "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
In rats, COQ6 was located within cell processes and the Golgi apparatus
of renal glomerular podocytes and in stria vascularis cells of the inner
ear, consistent with an oto-renal disease phenotype.
explanation: >-
COQ6 expression in inner-ear stria vascularis underlies the sensorineural
deafness of the oto-renal phenotype.
- category: Phenotypic abnormality
name: Cardiomyopathy
description: Cardiomyopathy occurs notably in neonatal COQ4 disease.
phenotype_term:
preferred_term: Cardiomyopathy
term:
id: HP:0001638
label: Cardiomyopathy
evidence:
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "cardiomyopathy (5/6)"
explanation: Cardiomyopathy was present in 5 of 6 neonatal COQ4 patients.
- category: Phenotypic abnormality
name: Lactic acidosis
description: >-
Hyperlactatemia/lactic acidosis is a common metabolic marker of impaired
oxidative phosphorylation.
phenotype_term:
preferred_term: Increased circulating lactate concentration
term:
id: HP:0002151
label: Increased circulating lactate concentration
evidence:
- reference: PMID:39398416
reference_title: "The Spectrum of clinical manifestations in newborns with the COQ4 mutation: case series and literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hyperlactatemia was one of the most common manifestations, accounting for
75% of cases (18/24).
explanation: >-
Hyperlactatemia was among the most common manifestations in neonatal COQ4
disease (18/24).
- category: Phenotypic abnormality
name: Cerebellar ataxia
subtype: COQ5
description: >-
Cerebellar ataxia of varying degree was the presenting feature in the three
siblings in whom biallelic COQ5 variants were first reported, alongside
encephalopathy, generalized tonic-clonic seizures and cognitive disability.
phenotype_term:
preferred_term: Cerebellar ataxia
term:
id: HP:0001251
label: Ataxia
evidence:
- reference: PMID:29044765
reference_title: "A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here, we report three female siblings of Iraqi-Jewish descent, who had
varying degrees of cerebellar ataxia, encephalopathy, generalized
tonic-clonic seizures, and cognitive disability.
explanation: >-
The COQ5 index family's presenting phenotype, reported with a measured
CoQ10 deficiency.
- category: Phenotypic abnormality
name: Progressive peripheral neuropathy
subtype: COQ7
description: >-
The late-onset COQ7 presentation is a progressive neuropathy with lower
extremity weakness and abnormal gait, distinct from the neonatal COQ7
presentation with severe neuromuscular, cardiorespiratory and renal
involvement.
phenotype_term:
preferred_term: Progressive peripheral neuropathy
term:
id: HP:0007133
label: Progressive peripheral neuropathy
evidence:
- reference: PMID:37392700
reference_title: "Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ(10) deficiency: Hypomorphic variants and two distinct disease entities."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The main clinical features included a neonatal-onset presentation with
severe neuromuscular, cardiorespiratory and renal involvement and a
late-onset disease presenting with progressive neuropathy, lower extremity
weakness, abnormal gait, and variable developmental delay.
explanation: >-
Reports progressive neuropathy with lower-limb weakness as the late-onset
COQ7 phenotype in a cohort of five new plus nine previously reported
patients.
- category: Phenotypic abnormality
name: Renal tubular dysfunction
subtype: COQ9
description: >-
Renal tubular dysfunction, rather than glomerular nephrotic syndrome, is the
renal manifestation recorded in the COQ9 index patient and is named in
MONDO's label for the COQ9 numbered form.
phenotype_term:
preferred_term: Renal tubular dysfunction
term:
id: HP:0000124
label: Renal tubular dysfunction
evidence:
- reference: PMID:19375058
reference_title: "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We genotyped a patient with primary coenzyme Q(10) deficiency who
presented with neonatal lactic acidosis and later developed multisytem
disease including intractable seizures, global developmental delay,
hypertrophic cardiomyopathy, and renal tubular dysfunction.
explanation: >-
Records renal tubular dysfunction in the patient with the biallelic
truncating COQ9 variant.
- category: Phenotypic abnormality
name: Optic atrophy
subtype: PDSS1
description: >-
Optic atrophy following sensorineural deafness was the presentation of a
PDSS1 sibling pair, consistent with the visual involvement reported when the
first steps of CoQ10 synthesis are impaired.
phenotype_term:
preferred_term: Optic atrophy
term:
id: HP:0000648
label: Optic atrophy
evidence:
- reference: PMID:33285023
reference_title: Missense PDSS1 mutations in CoenzymeQ10 synthesis cause optic atrophy and sensorineural deafness.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we describe two young sisters with sensorineural deafness followed by
optic atrophy, due to a novel homozygous pathogenic variant in PDSS1.
explanation: >-
Reports optic atrophy in two sisters with a biallelic PDSS1 variant.
genetic:
- name: COQ2
gene_term:
preferred_term: COQ2
term:
id: hgnc:25223
label: COQ2
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ2
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ2 (HGNC-approved name "coenzyme Q2, polyprenyltransferase", 4q21.23) acts
at the side-chain attachment step, joining the polyisoprenoid tail to
4-hydroxybenzoate. The gene-specific allelic series, genotype-phenotype
relationship and the separate multiple-system-atrophy susceptibility question
are curated in COQ2-Related_Primary_Coenzyme_Q10_Deficiency.
evidence:
- reference: PMID:17332895
reference_title: "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Transformation of yeast Deltacoq1 and Deltacoq2 strains by mutant yeast
COQ1 and mutant human COQ2 genes, respectively, resulted in defective
growth on respiratory medium, indicating that these mutations are indeed
the cause of OXPHOS deficiency.
explanation: >-
Yeast complementation establishes the patients' COQ2 and PDSS1/COQ1 alleles
as loss-of-function and as the cause of the OXPHOS defect.
- name: COQ4
gene_term:
preferred_term: COQ4
term:
id: hgnc:19693
label: COQ4
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ4
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ4 (9q34.11) is described by the cohort below as an essential component of
the multisubunit CoQ10 biosynthetic complex, which its authors read as
consistent with the uniformly severe neonatal phenotype. Later biochemistry
also assigns COQ4 a catalytic step, the C1 decarboxylation recorded on the
head-group modification node. The gene-specific
cohort is curated in COQ4-Related_Neonatal_Encephalomyopathy.
evidence:
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We identified five recessive missense mutations in COQ4 segregating with
disease in all four families.
explanation: >-
Recessive COQ4 missense alleles segregating with disease across four
families.
- reference: PMID:26185144
reference_title: "Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The early mortality in our cohort suggests that COQ4 is an essential
component of the multisubunit complex required for CoQ(10) biosynthesis.
explanation: >-
Source for describing COQ4 as a component of the multisubunit
biosynthetic complex.
- name: COQ5
gene_term:
preferred_term: COQ5
term:
id: hgnc:28722
label: COQ5
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ5
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ5 (HGNC-approved name "coenzyme Q5, methyltransferase", 12q24.31) is the
pathway's methyltransferase. The evidence base is two
probands, which is why ClinGen's grade is Moderate; a large tandem
duplication, a canonical splice-site variant and a missense variant are the
reported alleles.
evidence:
- reference: CGGV:assertion_9b9c2846-d034-46f4-87ba-525bed7efe9c-2024-07-10T160000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Three variants (1 large tandem duplication, 1 canonical splice-site, 1
missense) that have been reported in 2 probands in 2 publications (PMIDs:
29044765, 37599337) are included in this curation. The mechanism of
pathogenicity appears to be loss of function.
explanation: >-
ClinGen's summary of the COQ5 allelic evidence and of the loss-of-function
mechanism, and the basis for the Moderate grade recorded in the notes.
- name: COQ6
gene_term:
preferred_term: COQ6
term:
id: hgnc:20233
label: COQ6
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ6
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ6 (HGNC-approved name "coenzyme Q6, monooxygenase", 14q24.3) is the
pathway's monooxygenase, acting on the benzoquinone ring. The gene-specific
cohort and the oto-renal phenotype are curated in
COQ6-Related_Steroid-Resistant_Nephrotic_Syndrome.
evidence:
- reference: PMID:21540551
reference_title: "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we have identified 6 different mutations in coenzyme Q10 biosynthesis
monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity
mapping.
explanation: >-
Thirteen individuals from seven families carrying biallelic COQ6 variants.
- reference: PMID:21540551
reference_title: "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The deleterious effects of these human COQ6 mutations were validated by
their lack of complementation in coq6-deficient yeast.
explanation: >-
Yeast complementation establishes the patient alleles as loss of function.
- name: COQ8A
gene_term:
preferred_term: COQ8A
term:
id: hgnc:16812
label: COQ8A
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ8A
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ8A (1q42.13) is the paralogue of COQ8B and, like it, supports the
biosynthetic machinery rather than being assigned a catalytic step of the
pathway. HGNC records ADCK3 and CABC1 as previous symbols for this gene. The
cerebellar-ataxia phenotype is curated in
Autosomal_Recessive_Ataxia_Due_to_Ubiquinone_Deficiency. ClinGen has no
assertion for this gene: grepping the committed
cache/clingen/gene_validity.csv for COQ8A, ADCK3, CABC1 and HGNC:16812
returns no row.
evidence:
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: OTHER
quote_role: BACKGROUND
snippet: >-
ADCK4 was highly similar to ADCK3, which has been shown to participate in
coenzyme Q10 (CoQ10) biosynthesis.
explanation: >-
Records COQ8A, under its previous symbol ADCK3, as an established
participant in CoQ10 biosynthesis.
- name: COQ8B
gene_term:
preferred_term: COQ8B
term:
id: hgnc:19041
label: COQ8B
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ8B
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ8B (19q13.2) is the COQ8A paralogue, expressed in kidney podocytes. HGNC
records ADCK4 as its previous symbol. ClinGen lumps the COQ8B renal and
mitochondrial presentations into a single disease entity, whereas MONDO
keeps the renal concept as nephrotic syndrome type 9 under familial
idiopathic steroid-resistant nephrotic syndrome.
evidence:
- reference: CGGV:assertion_43b1c614-38c9-4729-8661-eecc0d24a364-2023-02-06T050000.000Z
supports: SUPPORT
evidence_source: OTHER
snippet: >-
While various names have been given to the constellation of features seen
in those with COQ8B -related disease, pathogenic variants in this gene
cause a primary mitochondrial disease.
explanation: >-
ClinGen's statement that the COQ8B presentations are one disease entity,
which is the lumping decision recorded in the notes.
- reference: PMID:24270420
reference_title: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift
mutation had partial remission following CoQ10 treatment.
explanation: >-
A biallelic COQ8B patient whose renal disease partially remitted on CoQ10,
supporting a causative and treatable relationship.
- name: COQ7
gene_term:
preferred_term: COQ7
term:
id: hgnc:2244
label: COQ7
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ7
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ7 (HGNC-approved name "coenzyme Q7, hydroxylase", 16p12.3) hydroxylates
demethoxyubiquinone. The report below delineates two presentations with an
emerging genotype-phenotype correlation and validates a yeast assay for COQ7
variants. ClinGen has no assertion for this gene: grepping the committed
cache/clingen/gene_validity.csv for COQ7 and for HGNC:2244 returns no row.
evidence:
- reference: PMID:37392700
reference_title: "Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ(10) deficiency: Hypomorphic variants and two distinct disease entities."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Overall, we define two distinct disease presentations of COQ7-related
disorder with emerging genotype-phenotype correlation and validate the use
of the yeast model for functional studies of COQ7 variants.
explanation: >-
The authors' conclusion that COQ7 produces two distinct presentations with
a genotype-phenotype correlation.
- reference: PMID:26084283
reference_title: "Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
We demonstrate that the coenzyme Q analogue 2,4-dihydroxybensoic acid
(2,4DHB) was able to specifically bypass the COQ7 deficiency, increase
cellular coenzyme Q levels and rescue the biochemical defect in patient
fibroblasts.
explanation: >-
Bypassing the COQ7 step in patient fibroblasts restores CoQ, which locates
the defect at that enzymatic step.
- name: COQ9
gene_term:
preferred_term: COQ9
term:
id: hgnc:25302
label: COQ9
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: COQ9
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
COQ9 (16q21) is a lipid-binding protein that partners COQ7; HGNC records
C16orf49 as its previous symbol. ClinGen carries two assertions for this
gene, Definitive against mitochondrial disease and Limited against Leigh
syndrome specifically, so the Definitive grade should not be read as a
Leigh-syndrome claim.
evidence:
- reference: PMID:19375058
reference_title: "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Site-directed mutagenesis targeting the equivalent residue in the yeast
Saccharomyces cerevisiae abolished respiratory growth.
explanation: >-
Functional confirmation that the truncating COQ9 allele abolishes
respiratory competence.
- reference: PMID:19375058
reference_title: "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cultured skin fibroblasts from the patient had a coenzyme Q(10)
biosynthetic rate of 11% of normal controls and accumulated an abnormal
metabolite that we believe to be a biosynthetic intermediate.
explanation: >-
Patient fibroblasts show a residual CoQ10 biosynthetic rate of 11% of
controls together with an accumulated upstream intermediate.
- name: PDSS1
gene_term:
preferred_term: PDSS1
term:
id: hgnc:17759
label: PDSS1
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: PDSS1
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
PDSS1 (HGNC-approved name "decaprenyl diphosphate synthase subunit 1",
10p12.1) is the human orthologue of yeast COQ1 and supplies the decaprenyl
diphosphate side chain; HGNC records TPRT as its previous symbol. The
committed ClinGen record grades it Moderate and names PDSS1-related primary
mitochondrial disease as its single disease entity.
evidence:
- reference: PMID:17332895
reference_title: "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A genome-wide search for homozygosity in family 1 identified a region of
chromosome 10 encompassing the gene prenyldiphosphate synthase, subunit 1
(PDSS1), which encodes the human ortholog of the yeast COQ1 gene, a key
enzyme of CoQ10 synthesis.
explanation: >-
Maps the first PDSS1 family to chromosome 10 and identifies the gene as the
human COQ1 orthologue.
- name: PDSS2
gene_term:
preferred_term: PDSS2
term:
id: hgnc:23041
label: PDSS2
relationship_type: CAUSATIVE
variant_origin: GERMLINE
subtype: PDSS2
inheritance:
- name: Autosomal Recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
notes: >-
PDSS2 (HGNC-approved name "decaprenyl diphosphate synthase subunit 2",
6q21) is the second subunit of the same side-chain synthase; HGNC records
C6orf210 as its previous symbol. The committed
cache/clingen/gene_validity.csv holds a single PDSS2 row, filed against Leigh
syndrome at Moderate rather than against a numbered CoQ10 deficiency class.
evidence:
- reference: PMID:17186472
reference_title: "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Biochemical assays with radiolabeled substrates indicated a severe defect
in decaprenyl diphosphate synthase in the patient's fibroblasts.
explanation: >-
Direct enzymatic confirmation that the biallelic PDSS2 variants impair
decaprenyl diphosphate synthase activity.
- reference: PMID:17186472
reference_title: "Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is the first description of pathogenic mutations in PDSS2 and confirms
the molecular and clinical heterogeneity of primary CoQ(10) deficiency.
explanation: >-
The first reported PDSS2 patient, presented by the authors as evidence of
the genetic heterogeneity of primary CoQ10 deficiency.
diagnosis:
- name: Molecular genetic testing
description: >-
Genome-wide molecular testing (WES/WGS or multigene panels) is the
recommended first-line diagnostic approach because there are no
pathognomonic blood, muscle, or imaging biomarkers and because early
diagnosis enables potentially disease-modifying treatment.
results: >-
Detection of biallelic pathogenic variants in a CoQ10 biosynthesis gene
confirms the molecular diagnosis and guides treatment.
diagnosis_term:
preferred_term: molecular genetic testing
term:
id: NCIT:C19770
label: Molecular Analysis
evidence:
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
An early genome-wide diagnostic approach is needed for expeditious
diagnosis of CoQ10 biosynthesis disorder because our study demonstrates
that there are no pathognomonic blood, muscle, or imaging biomarkers of
these diseases.
explanation: >-
Genome-wide molecular testing is recommended because no pathognomonic
biomarkers exist.
biochemical:
- name: Reduced muscle CoQ10 and respiratory chain activity
notes: >-
Biochemical support includes reduced CoQ10 levels in skeletal muscle and
reduced combined activities of respiratory chain complexes I+III and II+III
on muscle homogenates; plasma CoQ10 is not diagnostically reliable.
treatments:
- name: Coenzyme Q10 supplementation
description: >-
High-dose oral CoQ10 (ubiquinone/ubiquinol) supplementation is the only
disease-directed therapy. Early treatment can reverse or prevent renal
disease (around 30 mg/kg/day) and ameliorate neurologic features (up to
70 mg/kg/day); benefit is limited once irreversible organ injury is
established, and severe neonatal forms often respond poorly.
treatment_term:
preferred_term: coenzyme Q10 supplementation
term:
id: NCIT:C15425
label: Nutritional Supplementation
therapeutic_agent:
- preferred_term: coenzyme Q10
term:
id: CHEBI:46245
label: coenzyme Q10
evidence:
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We also demonstrate that early diagnosis and treatment of CoQ10
deficiency with oral supplementation (30 mg/kg/d) can reverse renal
manifestations and can completely prevent kidney disease over 10 years of
follow-up.
explanation: Early high-dose oral CoQ10 can reverse and prevent renal disease.
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We show that oral doses of CoQ10 up to 70 mg/kg/d were needed to
ameliorate neurologic features.
explanation: >-
Higher doses (up to 70 mg/kg/day) were required to ameliorate neurologic
features.
- name: Idebenone
description: >-
Idebenone, a synthetic CoQ10 analogue, was used as an adjunct to control
seizures in some patients (10-20 mg/kg/day).
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: idebenone
term:
id: CHEBI:31687
label: idebenone
evidence:
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Additional idebenone was required to control seizures in some cases, and
3 children with neonatal-onset neurologic disease died in early childhood
despite receiving high-dose oral CoQ10 from birth.
explanation: Idebenone was used as an adjunct to control seizures in some patients.
prevalence:
- population: General population
measure_type: POINT_PREVALENCE
prevalence_class: BAND_1_9_PER_100000
rate_high: 1.0
percentage: <0.001%
notes: >-
Primary CoQ10 deficiency is very rare, with prevalence/incidence estimated
at less than 1 per 100,000 population.
progression:
- phase: Neonatal/infantile severe multisystem disease
age_range: Neonatal to infantile onset
evidence:
- reference: PMID:39601013
reference_title: "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q(10) Biosynthesis Disorders."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Additional idebenone was required to control seizures in some cases, and
3 children with neonatal-onset neurologic disease died in early childhood
despite receiving high-dose oral CoQ10 from birth.
explanation: >-
Neonatal-onset neurologic disease has poor outcomes even with early
high-dose CoQ10.
animal_models:
- species: Mouse
genotype: Coq9 knockout
description: >-
The Coq9 knockout mouse recapitulates encephalopathy with cerebral gliosis
and spongiosis, modeling the neurologic injury of CoQ10 deficiency.
associated_phenotypes:
- Encephalopathy
- Cerebral gliosis
evidence:
- reference: PMID:36978966
reference_title: "Neuroimaging in Primary Coenzyme-Q(10)-Deficiency Disorders."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
CoQ10 deficiency exerts detrimental effects on the nervous system.
Potential consequences are neuronal death, neuroinflammation and cerebral
gliosis.
explanation: >-
Model and human evidence converge on neuronal death, neuroinflammation,
and cerebral gliosis as consequences of CoQ10 deficiency.
clinical_trials: []
datasets:
- accession: geo:GSE33941
title: Survival transcriptome in coenzyme Q deficiency syndrome
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_count: 35
publication: PMID:23533218
notes: Identified by GEO DataSets index search for Primary Coenzyme Q10 Deficiency (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
notes: >-
This is the umbrella entry for primary (biosynthesis) coenzyme Q10 deficiency,
which is the subset of CoQ10 deficiency caused by defects in the biosynthetic
pathway itself (PMID:37627647). Secondary CoQ10 deficiency, which PMID:37508007
describes as resulting from a wide variety of cellular dysfunctions not directly
linked to primary synthesis, is a different entity and is out of scope here.
Anchor. MONDO:0018151 carries "coenzyme Q10 deficiency, primary" and "CoQ10
deficiency, primary" among its exact synonyms, and all nine of its children are
the primary numbered forms COQ10D1 to COQ10D9, each asserting a single causal
gene in its OWL axioms. Searches for a secondary or a separate primary umbrella
class returned nothing: runoak -i ols:mondo search 'secondary coenzyme Q10
deficiency' and 'secondary CoQ10' both returned zero rows, and 't~coenzyme Q10
deficiency' returned exactly MONDO:0018151 plus those nine children. The
binding is therefore kept as an exactMatch-strength disease_term rather than
demoted to a broadMatch.
Numbered forms with their own dismech entries. COQ2 (MONDO:0011829) is curated
as COQ2-Related_Primary_Coenzyme_Q10_Deficiency, COQ4 (MONDO:0014562) as
COQ4-Related_Neonatal_Encephalomyopathy, COQ6 (MONDO:0013836) as
COQ6-Related_Steroid-Resistant_Nephrotic_Syndrome, and COQ8A (MONDO:0012784) as
Autosomal_Recessive_Ataxia_Due_to_Ubiquinone_Deficiency. Those four are
cross-referenced from has_subtypes rather than duplicated here. PDSS1, PDSS2,
COQ5, COQ7, COQ8B and COQ9 have no separate entry and are curated on this
umbrella.
COQ8B sits outside the MONDO umbrella. MONDO files the COQ8B disease as
MONDO:0014257 nephrotic syndrome type 9, under familial idiopathic
steroid-resistant nephrotic syndrome, so it is not one of MONDO:0018151's
children even though every source treats COQ8B as a CoQ10 biosynthesis gene.
That renal class is the subtype_term used on the COQ8B row.
HPDL is dispositioned elsewhere. PMID:36978966 counts HPDL among 11 CoQ10
biosynthesis disease genes, but MONDO gives the HPDL disease its own home as
MONDO:0033614 spastic paraplegia 83, filed under hereditary spastic paraplegia
and not under coenzyme Q10 deficiency, and ClinGen's only HPDL assertion is
Moderate against Leigh syndrome. HPDL therefore gets no subtype row on this
umbrella. Searches run: runoak -i ols:mondo search 'HPDL', '4-hydroxyphenylpyruvate
dioxygenase like' (both zero rows) and 'spastic paraplegia 83'.
ClinGen's COQ6 row names the wrong numbered form. The committed
gene_validity.csv row for COQ6 gives its disease as "primary coenzyme Q10
deficiency 8" / MONDO:0014754, but MONDO:0014754 is the COQ7 form (its
definition names COQ7 and its axiom asserts hgnc:2244), while COQ6's form is
COQ10D6 / MONDO:0013836. That row is therefore not cited anywhere in this
entry; the COQ6 claims rest on PMID:21540551 instead.
Orphanet could not be consulted. MONDO:0018151 carries Orphanet:35656 as an
xref, references_cache holds no ORPHA_35656.md, and just fetch-reference
ORPHA:35656 returns "No source found for reference type", so no Orphanet content
is used or asserted here.
References & Deep Research
Deep Research
1Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.
Falcon
▸
1. Disease Information
1.1 What is the disease?
Definition (current understanding): GeneReviews (2023) defines the term primary CoQ10 deficiency as “the group of conditions characterized by a reduction of CoQ10 levels in tissues or cultured cells associated with biallelic pathogenic variants in one of the ten genes involved in the biosynthesis of CoQ10.” (salviati2023primarycoenzymeq10b pages 1-3)
Treatability concept: Multiple recent reviews emphasize it is potentially treatable if recognized early, because once critical-organ injury (kidney/CNS) is established, recovery is limited. (mantle2023primarycoenzymeq10 pages 1-2, mantle2024efficacyandsafety pages 2-3)
1.2 Key identifiers
- MONDO: MONDO:0018151 (carmody2023themedicalaction pages 5-8)
- MAxO treatment mapping: MAXO:0010012 “coenzyme Q10 supplementation”; definition “Addition of coenzyme Q10 to the diet,” input chemical CHEBI:46245 (coenzyme Q10 / coenzyme Q); explicitly stated to treat diseases including MONDO:0018151 (carmody2023themedicalaction pages 5-8)
Not retrieved in tool evidence: OMIM disease number(s), Orphanet ORPHA code, ICD-10/ICD-11, MeSH. These likely exist but were not present in the obtained full-text extracts.
1.3 Synonyms / alternative names
- Primary coenzyme Q10 deficiency; primary CoQ10 deficiency; primary ubiquinone deficiency (salviati2023primarycoenzymeq10b pages 1-3)
1.4 Evidence source type
The knowledge base content here is derived from: - Aggregated disease-level syntheses (GeneReviews-style overview and narrative reviews) (salviati2023primarycoenzymeq10b pages 1-3, mantle2023primarycoenzymeq10 pages 1-2) - Human cohort/case-series clinical evidence (single-center cohort of genetically confirmed cases; neonatal COQ4 case series + literature review) (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
2. Etiology
2.1 Disease causal factors
Genetic cause: PCoQD results from pathogenic variants in nuclear genes encoding CoQ10 biosynthesis proteins; recent sources repeatedly emphasize biallelic pathogenic variants (autosomal recessive pattern). (salviati2023primarycoenzymeq10b pages 1-3, salviati2023primarycoenzymeq10b pages 5-7)
2.2 Risk factors
- Genetic: Presence of biallelic pathogenic variants in one of the canonical CoQ10 biosynthesis genes (see below) is causal. (salviati2023primarycoenzymeq10b pages 1-3)
- Environmental: No specific environmental risk factors were identified in the retrieved evidence; by definition PCoQD is a primary genetic biosynthesis disorder.
2.3 Protective factors
No validated protective genetic variants or environmental protective exposures were identified in the retrieved evidence.
2.4 Gene–environment interactions
Not specifically described in the retrieved sources.
3. Phenotypes
3.1 Major phenotype domains (with frequencies when available)
PCoQD is clinically heterogeneous, with core involvement of the CNS, kidney, muscle, and heart. (wahedi2024clinicalfeaturesbiochemistry pages 1-2, salviati2023primarycoenzymeq10b pages 3-5)
Neurologic phenotypes - Encephalopathy, developmental delay/regression, movement disorders, epilepsy, intellectual disability (munch2023neuroimaginginprimary pages 1-3) - In a 14-patient genetically confirmed cohort: seizures in 8/14 (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
Renal phenotypes - Steroid-resistant nephrotic syndrome (SRNS) and progression to ESKD are key manifestations in several gene-specific forms; in the 14-patient cohort, SRNS in 3/14. (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
Metabolic / laboratory phenotypes - Hyperlactatemia: 14-patient cohort had lactate elevated in 5/12 tested (wahedi2024clinicalfeaturesbiochemistry pages 2-3) - Neonatal COQ4 series: hyperlactatemia 18/24 (75%) (reported in abstract; paper retrieved but not fully evidence-extracted here beyond cohort stats in artifact) (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
Neuroimaging phenotypes (MRI patterns) MRI is emphasized as central for assessing neurologic injury. The neuroimaging review states: “Brain magnetic resonance imaging (MRI) is the most important tool for diagnostic evaluation of neurological damage in individuals with CoQ10 deficiency.” (munch2023neuroimaginginprimary pages 1-3) - Common patterns across genes: leukoencephalopathy/white matter changes, cerebral/cerebellar atrophy, Leigh-like basal ganglia/brainstem lesions, stroke-like lesions, lactate peaks on MR spectroscopy. (munch2023neuroimaginginprimary pages 3-4, munch2023neuroimaginginprimary pages 10-12) - COQ8A: cerebellar atrophy is reported in 94% of patients summarized (munch2023neuroimaginginprimary pages 6-9)
3.2 Suggested HPO terms (non-exhaustive; evidence-aligned)
(These are ontology suggestions based on the described phenotypes; not explicitly enumerated in the cited papers.) - HP:0001250 Seizures; HP:0001263 Global developmental delay; HP:0001252 Muscular hypotonia; HP:0001251 Ataxia; HP:0001272 Cerebellar atrophy; HP:0004372 Status epilepticus; HP:0001257 Spasticity; HP:0001290 Generalized hypotonia; HP:0003070 Renal insufficiency; HP:0000100 Nephrotic syndrome; HP:0000510 Retinopathy; HP:0000608 Optic atrophy; HP:0001644 Cardiomyopathy.
3.3 Quality of life impact
Direct QoL instrument data (EQ-5D/SF-36/PROMIS) were not located in the retrieved evidence; however, neurological disability (developmental delay, epilepsy, ataxia) and progression to renal failure imply major functional impairment. (salviati2023primarycoenzymeq10b pages 3-5, wahedi2024clinicalfeaturesbiochemistry pages 1-2)
4. Genetic / Molecular Information
4.1 Causal genes (core list)
GeneReviews (2023) emphasizes ten genes; a neuroimaging review includes 11 disease genes (adding HPDL). (salviati2023primarycoenzymeq10b pages 1-3, munch2023neuroimaginginprimary pages 1-3)
Canonical CoQ biosynthesis genes (GeneReviews): - PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9 (salviati2023primarycoenzymeq10b pages 1-3)
Additional disease gene in neuroimaging review: - HPDL (munch2023neuroimaginginprimary pages 1-3)
4.2 Pathogenic variants
Variant-level catalogs (ClinVar allele frequencies; ACMG/AMP classifications per-variant; founder variants) were not extractable from the retrieved evidence chunks. However, the disease mechanism requires biallelic pathogenic variants in the relevant genes. (salviati2023primarycoenzymeq10b pages 5-7)
4.3 Modifier genes / epigenetics / chromosomal abnormalities
Not described in the retrieved sources.
5. Environmental Information
PCoQD is a primary genetic biosynthesis defect; no specific toxins, lifestyle factors, or infectious triggers were supported in the retrieved evidence.
6. Mechanism / Pathophysiology
6.1 Key concepts: CoQ10 functions
Recent reviews stress CoQ10’s roles beyond OXPHOS.
Direct abstract quote (Mantle et al., 2023, Antioxidants; Aug 2023; DOI: https://doi.org/10.3390/antiox12081652): - “Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial.” (mantle2023primarycoenzymeq10 pages 1-2)
Neuroimaging review (Mar 2023; DOI: https://doi.org/10.3390/antiox12030718) highlights: - CoQ10’s best-known role is electron transfer/ATP synthesis, but “there are many other cellular pathways that also depend on the CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidation).” (munch2023neuroimaginginprimary pages 1-3)
Biochemistry review (Jul 2023; DOI: https://doi.org/10.3390/antiox12071469): CoQ is electron acceptor for multiple dehydrogenases (DHODH, ETFDH, SQOR, etc.) and contributes to ferroptosis protection via the FSP1 system. (staiano2023biosynthesisdeficiencyand pages 1-2)
6.2 Causal chain (trigger → molecular dysfunction → tissue injury → clinical phenotype)
Upstream: biallelic pathogenic variants in CoQ biosynthesis genes → reduced CoQ10 in tissues/cultured cells. (salviati2023primarycoenzymeq10b pages 1-3)
Midstream: impaired electron transfer between respiratory chain complexes → impaired oxidative phosphorylation, reduced ATP production (especially affecting high-energy organs), plus disruption of non-bioenergetic CoQ roles (redox homeostasis, ferroptosis defense, sulfide oxidation; dehydrogenase-linked metabolism). (munch2023neuroimaginginprimary pages 1-3, staiano2023biosynthesisdeficiencyand pages 1-2)
Downstream: neurologic injury is conceptualized as involving “neuronal death, neuroinflammation and cerebral gliosis.” (munch2023neuroimaginginprimary pages 1-3)
6.3 Cellular processes and pathways (suggested ontology terms)
Evidence-based processes include: - Oxidative phosphorylation impairment; redox imbalance/oxidative stress; neuroinflammation and gliosis; ferroptosis-related defenses; sulfide oxidation dependence. (munch2023neuroimaginginprimary pages 1-3)
Suggested GO biological process terms (ontology suggestions based on described mechanisms): - GO:0006119 oxidative phosphorylation; GO:0006979 response to oxidative stress; GO:0006954 inflammatory response; GO:0097468 neuronal death; GO:0097034 glial cell activation; GO:0070228 regulation of ferroptosis; GO:1902600 hydrogen sulfide metabolic process.
Suggested CL cell types (ontology suggestions): - CL:0000540 neuron; CL:0000127 astrocyte; CL:0000129 microglial cell; CL:0002301 podocyte (for CoQ nephropathy/SRNS contexts).
7. Anatomical Structures Affected
7.1 Organ systems
- Central nervous system (encephalopathy, epilepsy, cerebellar ataxia/atrophy; MRI patterns) (munch2023neuroimaginginprimary pages 1-3, munch2023neuroimaginginprimary pages 6-9)
- Kidney (SRNS/ESKD; potentially reversible if treated early in some cases) (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
- Heart (cardiomyopathy) (mantle2024efficacyandsafety pages 2-3)
- Eye/optic nerve/retina (optic atrophy/retinopathy in subsets) (mantle2024efficacyandsafety pages 2-3)
7.2 Suggested UBERON terms (ontology suggestions)
- Cerebellum (UBERON:0002037), brain (UBERON:0000955), kidney (UBERON:0002113), heart (UBERON:0000948), retina (UBERON:0000966), optic nerve (UBERON:0001778).
7.3 Subcellular localization
Primary locus of dysfunction is mitochondrial: CoQ10 is a lipid molecule of cellular membranes with key respiratory chain function. (munch2023neuroimaginginprimary pages 1-3) Suggested GO cellular component: mitochondrion (GO:0005739), inner mitochondrial membrane (GO:0005743).
8. Temporal Development
8.1 Onset
Onset is highly variable (neonatal to adulthood) across CoQ biosynthesis disorders. (munch2023neuroimaginginprimary pages 1-3)
8.2 Progression
GeneReviews summary indicates severe neonatal multisystem disease often has poor outcome, while later-onset cases show better response to high-dose supplementation. (salviati2023primarycoenzymeq10b pages 3-5)
9. Inheritance and Population
9.1 Inheritance
GeneReviews-style text emphasizes biallelic pathogenic variants (autosomal recessive). (salviati2023primarycoenzymeq10b pages 1-3)
9.2 Epidemiology
Recent pediatric-focused review states prevalence/incidence were estimated as “less than 1 per 100,000 population.” (mantle2024efficacyandsafety pages 2-3)
A different review estimated “approximately 120,000 patients worldwide,” but this appears to be a broad estimate rather than registry-derived epidemiology. (mantle2023primarycoenzymeq10 pages 1-2)
9.3 Demographics / geographic distribution
Neonatal COQ4 literature review reported that “Half of the cases are Chinese.” (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
10. Diagnostics
10.1 Biochemical testing
GeneReviews (2023) indicates biochemical testing now has a limited role, used when molecular results are inconclusive or to support VUS interpretation. Key supportive findings include: - “Reduced levels of CoQ10 in skeletal muscle” - “Reduced activities of complex I+III and II+III of the mitochondrial respiratory chain on frozen muscle homogenates” (salviati2023primarycoenzymeq10b pages 5-7)
The same GeneReviews extract states plasma CoQ10 is not diagnostically useful. (salviati2023primarycoenzymeq10b pages 5-7)
A 2024 cohort used high-performance liquid chromatography quantification of CoQ10 in muscle and PBMNCs and respiratory chain enzyme assays. (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
10.2 Genetic testing
Because “there are no pathognomonic blood, muscle, or imaging biomarkers of these diseases,” an “early genome-wide diagnostic approach” is recommended for expeditious diagnosis. (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
In the neonatal COQ4 series, 20/24 were diagnosed by whole exome sequencing. (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
10.3 Imaging
MRI is emphasized as most important for assessing neurologic damage in CoQ10 deficiency. (munch2023neuroimaginginprimary pages 1-3)
10.4 Differential diagnosis
GeneReviews excerpt notes secondary CoQ10 deficiency causes to consider, including respiratory chain defects and multiple acyl-CoA dehydrogenase deficiency. (salviati2023primarycoenzymeq10b pages 5-7)
11. Outcome / Prognosis
11.1 Prognosis statistics (recent)
Neonatal COQ4 mutation series (Frontiers in Pediatrics, Sep 2024; DOI: https://doi.org/10.3389/fped.2024.1410133): - Mortality: Chinese 9/12 (75%) vs other regions 11/12 (91.7%) (P=0.27) - Mean survival time 60.0 ± 98.0 days (95% CI 0–252 days) - CoQ10 treatment: 9/24 received CoQ10, and all 4 surviving patients received CoQ10 supplementation (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
Single-center cohort (Neurology Genetics, Dec 2024; DOI: https://doi.org/10.1212/nxg.0000000000200209): - Despite high-dose CoQ10 from birth, “3 children with neonatal-onset neurologic disease died in early childhood” (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
11.2 Prognostic factors
GeneReviews excerpt indicates severity/onset matters: “Children with severe multisystem CoQ10 deficiency respond poorly to treatment and generally die within the neonatal period or in the first year of life,” whereas “Individuals with later-onset disease show better response to supplementation with high-dose oral CoQ10.” (salviati2023primarycoenzymeq10b pages 3-5)
12. Treatment
12.1 Pharmacotherapy (current standard)
Oral CoQ10 supplementation is consistently described as the principal/only disease-directed therapy in recent reviews.
Direct abstract quote (Mantle & Hargreaves, Apr 2024; DOI: https://doi.org/10.3390/antiox13050530): - “The only treatment for primary CoQ10 deficiency is oral supplementation with CoQ10,” with typical doses in clinical studies “10–30 mg/kg/day.” (mantle2024efficacyandsafety pages 2-3)
Cohort dosing/outcome evidence (Dec 2024 cohort): - “oral doses of CoQ10 up to 70 mg/kg/d were needed to ameliorate neurologic features” (wahedi2024clinicalfeaturesbiochemistry pages 1-2) - “early diagnosis and treatment… (30 mg/kg/d) can reverse renal manifestations and can completely prevent kidney disease over 10 years of follow-up.” (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
Adjunct therapy: - “Additional idebenone was required to control seizures in some cases” with idebenone used at 10–20 mg/kg/day in that cohort. (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
12.2 Treatment monitoring / real-world implementation
PBMNC CoQ10 monitoring can demonstrate absorption and track response; the cohort reported PBMNC increases (examples) of +352%, +146% then +320%, +221% in individual patients. (wahedi2024clinicalfeaturesbiochemistry pages 2-3)
Image-based evidence: Wahedi et al. include tables summarizing patient-level dosing/outcomes and a figure showing serial PBMNC CoQ10 monitoring. (wahedi2024clinicalfeaturesbiochemistry media 455edda8, wahedi2024clinicalfeaturesbiochemistry media 782a63c5, wahedi2024clinicalfeaturesbiochemistry media 84940300)
12.3 Clinical trials landscape
A recent pediatric review notes “no formal clinical trials (randomised controlled or otherwise) have been reported” for primary CoQ10 deficiency treatment. (mantle2024efficacyandsafety pages 2-3)
12.4 Suggested MAXO terms
- MAXO:0010012 coenzyme Q10 supplementation (carmody2023themedicalaction pages 5-8)
- Additional suggested actions (ontology suggestions): antiseizure therapy; renal transplantation; ACE inhibitor therapy for proteinuria (not fully evidenced in retrieved 2023–2024 texts here).
13. Prevention
Primary prevention is not applicable in the classic public-health sense because PCoQD is inherited.
Secondary/tertiary prevention concept (early detection + early therapy): Multiple sources emphasize early diagnosis and prompt high-dose supplementation to prevent irreversible organ damage. (wahedi2024clinicalfeaturesbiochemistry pages 1-2, mantle2024efficacyandsafety pages 2-3)
Genetic counseling and cascade testing are implied by autosomal recessive inheritance, but explicit guideline text was not retrieved.
14. Other Species / Natural Disease
No naturally occurring veterinary disease analogs were identified in the retrieved evidence.
15. Model Organisms and Experimental Systems
15.1 Yeast and in vitro systems
A diagnostic-methods review states: “Most of the information about the CoQ biosynthesis pathway comes from yeast.” (rodriguezaguilera2017biochemicalassessmentof pages 1-3)
Human fibroblasts are widely used to assess CoQ10 content and functional rescue; the same review notes that “CoQ10 but not other quinones can restore mitochondrial function in deficient human fibroblasts.” (rodriguezaguilera2017biochemicalassessmentof pages 1-3)
15.2 Mouse models (examples explicitly mentioned)
- Coq9 knock-out mouse: “showed cerebral gliosis and spongiosis” (munch2023neuroimaginginprimary pages 1-3)
- Coq7 deficiency in mice: “induced a microglial metabolic reprogramming” (munch2023neuroimaginginprimary pages 1-3)
- Additional models summarized in 2024 mitochondrial disease muscle study: Pdss2 deficiency mouse, Coq7 knockout mice, Coq8a (Adck3) null mouse (slowly progressive cerebellar ataxia), Coq9 knockouts (encephalopathy), and Adck2+/− model (hernandez‐camacho2024prenatalandprogressive pages 1-2)
Recent developments and expert synthesis (2023–2024 emphasis)
- Shift toward genome-wide diagnosis: A 2024 cohort argues for early genome-wide testing because there are no pathognomonic biomarkers and because renal disease may be preventable with early treatment. (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
- Dose escalation for neurologic benefit: The same cohort reports neurologic improvement sometimes requires up to 70 mg/kg/day, higher than historical “10–30 mg/kg/day” frequently cited in review literature. (wahedi2024clinicalfeaturesbiochemistry pages 1-2, mantle2024efficacyandsafety pages 2-3)
- Monitoring via PBMNC CoQ10: Serial PBMNC monitoring is increasingly used to document absorption/biological exposure in real-world clinical management. (wahedi2024clinicalfeaturesbiochemistry pages 2-3, wahedi2024clinicalfeaturesbiochemistry media 455edda8)
- Expanded mechanistic framing: Reviews emphasize non-bioenergetic roles (ferroptosis, sulfide oxidation, redox homeostasis), supporting why phenotypic heterogeneity may not be explained by ATP deficiency alone. (munch2023neuroimaginginprimary pages 1-3, staiano2023biosynthesisdeficiencyand pages 1-2)
Limitations of this report (evidence availability)
- PMIDs: Many retrieved sources were available with DOI/URL but PMIDs were not present in the extracted text chunks; therefore PMID-level citations could not be systematically provided.
- ICD/Orphanet/MeSH/OMIM numbers: Not retrieved in the available evidence extracts; MONDO and MAxO mappings were retrieved and reported. (carmody2023themedicalaction pages 5-8)
- Variant catalog details (allele frequencies; ClinVar classifications): Not available in retrieved evidence.
Key URLs (most recent/authoritative in this run)
- Wahedi et al., Neurology Genetics (Dec 2024): https://doi.org/10.1212/nxg.0000000000200209 (wahedi2024clinicalfeaturesbiochemistry pages 1-2)
- Salviati et al., GeneReviews-style overview (2023): (source text retrieved without a stable GeneReviews URL in evidence) (salviati2023primarycoenzymeq10b pages 1-3)
- Mantle et al., Antioxidants (Aug 2023): https://doi.org/10.3390/antiox12081652 (mantle2023primarycoenzymeq10 pages 1-2)
- Münch et al., Antioxidants (Mar 2023): https://doi.org/10.3390/antiox12030718 (munch2023neuroimaginginprimary pages 1-3)
- Mantle & Hargreaves, Antioxidants (Apr 2024): https://doi.org/10.3390/antiox13050530 (mantle2024efficacyandsafety pages 2-3)
- MAxO ontology paper, Med (Dec 2023): https://doi.org/10.1016/j.medj.2023.10.003 (carmody2023themedicalaction pages 5-8)
References
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(salviati2023primarycoenzymeq10b pages 1-3): L Salviati, E Trevisson, C Agosto, M Doimo, and P Navas. Primary coenzyme q10 deficiency overview. Unknown journal, 2023.
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(carmody2023themedicalaction pages 5-8): Leigh C. Carmody, Michael A. Gargano, Sabrina Toro, Nicole A. Vasilevsky, Margaret P. Adam, Hannah Blau, Lauren E. Chan, David Gomez-Andres, Rita Horvath, Megan L. Kraus, Markus S. Ladewig, David Lewis-Smith, Hanns Lochmüller, Nicolas A. Matentzoglu, Monica C. Munoz-Torres, Catharina Schuetz, Berthold Seitz, Morgan N. Similuk, Teresa N. Sparks, Timmy Strauss, Emilia M. Swietlik, Rachel Thompson, Xingmin Aaron Zhang, Christopher J. Mungall, Melissa A. Haendel, and Peter N. Robinson. The medical action ontology: a tool for annotating and analyzing treatments and clinical management of human disease. Med, 4:913-927.e3, Dec 2023. URL: https://doi.org/10.1016/j.medj.2023.10.003, doi:10.1016/j.medj.2023.10.003. This article has 15 citations and is from a domain leading peer-reviewed journal.
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(wahedi2024clinicalfeaturesbiochemistry pages 1-2): Azizia Wahedi, Sniya Sudhakar, Amanda Lam, Jose Ignacio Rodriguez Ciancio, Philippa Mills, Paul Gissen, Alice Gardham, Jogesh Kapadia, Jane Hassell, Simon Heales, and Shamima Rahman. Clinical features, biochemistry, imaging, and treatment response in a single-center cohort with coenzyme q 10 biosynthesis disorders. Dec 2024. URL: https://doi.org/10.1212/nxg.0000000000200209, doi:10.1212/nxg.0000000000200209. This article has 6 citations.
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(salviati2023primarycoenzymeq10b pages 3-5): L Salviati, E Trevisson, C Agosto, M Doimo, and P Navas. Primary coenzyme q10 deficiency overview. Unknown journal, 2023.
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(mantle2023primarycoenzymeq10 pages 1-2): David Mantle, Lauren Millichap, Jesus Castro-Marrero, and Iain P. Hargreaves. Primary coenzyme q10 deficiency: an update. Antioxidants, 12:1652, Aug 2023. URL: https://doi.org/10.3390/antiox12081652, doi:10.3390/antiox12081652. This article has 51 citations.
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(mantle2024efficacyandsafety pages 2-3): David Mantle and Iain Parry Hargreaves. Efficacy and safety of coenzyme q10 supplementation in neonates, infants and children: an overview. Antioxidants, 13:530, Apr 2024. URL: https://doi.org/10.3390/antiox13050530, doi:10.3390/antiox13050530. This article has 14 citations.
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(munch2023neuroimaginginprimary pages 1-3): Juliane Münch, Jannik Prasuhn, Lucia Laugwitz, Cheuk-Wing Fung, Brian H.-Y. Chung, Marcello Bellusci, Ertan Mayatepek, Dirk Klee, and Felix Distelmaier. Neuroimaging in primary coenzyme-q10-deficiency disorders. Antioxidants, 12:718, Mar 2023. URL: https://doi.org/10.3390/antiox12030718, doi:10.3390/antiox12030718. This article has 17 citations.
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(munch2023neuroimaginginprimary pages 3-4): Juliane Münch, Jannik Prasuhn, Lucia Laugwitz, Cheuk-Wing Fung, Brian H.-Y. Chung, Marcello Bellusci, Ertan Mayatepek, Dirk Klee, and Felix Distelmaier. Neuroimaging in primary coenzyme-q10-deficiency disorders. Antioxidants, 12:718, Mar 2023. URL: https://doi.org/10.3390/antiox12030718, doi:10.3390/antiox12030718. This article has 17 citations.
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(salviati2023primarycoenzymeq10b pages 5-7): L Salviati, E Trevisson, C Agosto, M Doimo, and P Navas. Primary coenzyme q10 deficiency overview. Unknown journal, 2023.
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(wahedi2024clinicalfeaturesbiochemistry pages 2-3): Azizia Wahedi, Sniya Sudhakar, Amanda Lam, Jose Ignacio Rodriguez Ciancio, Philippa Mills, Paul Gissen, Alice Gardham, Jogesh Kapadia, Jane Hassell, Simon Heales, and Shamima Rahman. Clinical features, biochemistry, imaging, and treatment response in a single-center cohort with coenzyme q 10 biosynthesis disorders. Dec 2024. URL: https://doi.org/10.1212/nxg.0000000000200209, doi:10.1212/nxg.0000000000200209. This article has 6 citations.
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(munch2023neuroimaginginprimary pages 6-9): Juliane Münch, Jannik Prasuhn, Lucia Laugwitz, Cheuk-Wing Fung, Brian H.-Y. Chung, Marcello Bellusci, Ertan Mayatepek, Dirk Klee, and Felix Distelmaier. Neuroimaging in primary coenzyme-q10-deficiency disorders. Antioxidants, 12:718, Mar 2023. URL: https://doi.org/10.3390/antiox12030718, doi:10.3390/antiox12030718. This article has 17 citations.
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(mantle2023primarycoenzymeq10 pages 2-4): David Mantle, Lauren Millichap, Jesus Castro-Marrero, and Iain P. Hargreaves. Primary coenzyme q10 deficiency: an update. Antioxidants, 12:1652, Aug 2023. URL: https://doi.org/10.3390/antiox12081652, doi:10.3390/antiox12081652. This article has 51 citations.
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(hargreaves2023primarycoenzymeq10 pages 2-4): Iain Parry Hargreaves and David Mantle. Primary coenzyme q10 deficiency: an update. Unknown journal, May 2023. URL: https://doi.org/10.20944/preprints202305.1024.v1, doi:10.20944/preprints202305.1024.v1.
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(hargreaves2023primarycoenzymeq10 pages 1-2): Iain Parry Hargreaves and David Mantle. Primary coenzyme q10 deficiency: an update. Unknown journal, May 2023. URL: https://doi.org/10.20944/preprints202305.1024.v1, doi:10.20944/preprints202305.1024.v1.
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(munch2023neuroimaginginprimary pages 10-12): Juliane Münch, Jannik Prasuhn, Lucia Laugwitz, Cheuk-Wing Fung, Brian H.-Y. Chung, Marcello Bellusci, Ertan Mayatepek, Dirk Klee, and Felix Distelmaier. Neuroimaging in primary coenzyme-q10-deficiency disorders. Antioxidants, 12:718, Mar 2023. URL: https://doi.org/10.3390/antiox12030718, doi:10.3390/antiox12030718. This article has 17 citations.
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(staiano2023biosynthesisdeficiencyand pages 1-2): Carmine Staiano, Laura García-Corzo, David Mantle, Nadia Turton, Lauren E. Millichap, Gloria Brea-Calvo, and Iain Hargreaves. Biosynthesis, deficiency, and supplementation of coenzyme q. Antioxidants, 12:1469, Jul 2023. URL: https://doi.org/10.3390/antiox12071469, doi:10.3390/antiox12071469. This article has 24 citations.
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(wahedi2024clinicalfeaturesbiochemistry media 455edda8): Azizia Wahedi, Sniya Sudhakar, Amanda Lam, Jose Ignacio Rodriguez Ciancio, Philippa Mills, Paul Gissen, Alice Gardham, Jogesh Kapadia, Jane Hassell, Simon Heales, and Shamima Rahman. Clinical features, biochemistry, imaging, and treatment response in a single-center cohort with coenzyme q 10 biosynthesis disorders. Dec 2024. URL: https://doi.org/10.1212/nxg.0000000000200209, doi:10.1212/nxg.0000000000200209. This article has 6 citations.
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(wahedi2024clinicalfeaturesbiochemistry media 782a63c5): Azizia Wahedi, Sniya Sudhakar, Amanda Lam, Jose Ignacio Rodriguez Ciancio, Philippa Mills, Paul Gissen, Alice Gardham, Jogesh Kapadia, Jane Hassell, Simon Heales, and Shamima Rahman. Clinical features, biochemistry, imaging, and treatment response in a single-center cohort with coenzyme q 10 biosynthesis disorders. Dec 2024. URL: https://doi.org/10.1212/nxg.0000000000200209, doi:10.1212/nxg.0000000000200209. This article has 6 citations.
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(wahedi2024clinicalfeaturesbiochemistry media 84940300): Azizia Wahedi, Sniya Sudhakar, Amanda Lam, Jose Ignacio Rodriguez Ciancio, Philippa Mills, Paul Gissen, Alice Gardham, Jogesh Kapadia, Jane Hassell, Simon Heales, and Shamima Rahman. Clinical features, biochemistry, imaging, and treatment response in a single-center cohort with coenzyme q 10 biosynthesis disorders. Dec 2024. URL: https://doi.org/10.1212/nxg.0000000000200209, doi:10.1212/nxg.0000000000200209. This article has 6 citations.
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(rodriguezaguilera2017biochemicalassessmentof pages 1-3): Juan Rodríguez-Aguilera, Ana Cortés, Daniel Fernández-Ayala, and Plácido Navas. Biochemical assessment of coenzyme q10 deficiency. Journal of Clinical Medicine, 6:27, Mar 2017. URL: https://doi.org/10.3390/jcm6030027, doi:10.3390/jcm6030027. This article has 71 citations.
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(hernandez‐camacho2024prenatalandprogressive pages 1-2): Juan Diego Hernández‐Camacho, Cristina Vicente‐García, Lorena Ardila‐García, Ana Padilla‐Campos, Guillermo López‐Lluch, Carlos Santos‐Ocaña, Peter S. Zammit, Jaime J. Carvajal, Plácido Navas, and Daniel J.M. Fernández‐Ayala. Prenatal and progressive coenzyme q10 administration to mitigate muscle dysfunction in mitochondrial disease. Journal of Cachexia, Sarcopenia and Muscle, 15:2402-2416, Oct 2024. URL: https://doi.org/10.1002/jcsm.13574, doi:10.1002/jcsm.13574. This article has 8 citations and is from a domain leading peer-reviewed journal.
