IEMbase 0143: DGUOK-related mitochondrial deoxyguanosine kinase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 143 |
| Nosology | 9.1.03.01 |
| Gene | DGUOK |
| External IDs | OMIM:251880; OMIM:601465; ORPHA:494348 |
| Generated mapping | CANDIDATE to Mitochondrial_DNA_Depletion_Syndrome_7.yaml |
| Candidate DisMech targets | No valid DGUOK/MTDPS3 target found |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as DGUOK-related mitochondrial deoxyguanosine kinase deficiency, with alternate labels mitochondrial DNA depletion syndrome 3 hepatocerebral type and autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions 4. Treatability is marked unknown.
The IEMbase profile is hepatocerebral. Biochemical rows include decreased respiratory-chain complex activity, increased gamma-glutamyl transpeptidase, increased transaminases, increased alpha-fetoprotein, increased ferritin, hypoglycemia, increased plasma and CSF lactate, and decreased muscle cytochrome C oxidase in later-onset disease. Clinical rows include hepatomegaly, jaundice, liver failure, cholestasis, portal hypertension, iron overload, hepatocellular carcinoma or hepatoblastoma, hypotonia, myopathy, neurological symptoms, nystagmus, ophthalmoplegia, ptosis, psychomotor regression, and death.
DisMech phenotype coverage
The generated candidate, Mitochondrial_DNA_Depletion_Syndrome_7.yaml, is not
the same disease. That local entry is TWNK-related mitochondrial DNA depletion
syndrome 7 / infantile-onset spinocerebellar ataxia, with a Twinkle helicase
mechanism. It overlaps at the broad mtDNA-depletion and hepatocerebral wording
level, but its causal gene and disease identity differ from DGUOK/MTDPS3.
No exact local DGUOK, deoxyguanosine kinase, or MTDPS3 disease target was found.
Concordance and completeness
Judgement: generated false-positive candidate; true local disease gap.
The CANDIDATE status is understandable because both records sit in the mitochondrial DNA depletion family and include liver/brain disease. It should not be accepted as coverage because DGUOK nucleotide-salvage deficiency and TWNK helicase deficiency are distinct mechanisms and MONDO leaves.
Curation actions
- Keep this record unmapped for now.
- Reject
Mitochondrial_DNA_Depletion_Syndrome_7.yamlas an exact target. - Future curation should add a DGUOK/MTDPS3 hepatocerebral mtDNA depletion entry with respiratory-chain deficiency, lactic acidosis, hepatic failure, hypoglycemia, cholestasis/portal hypertension, neurologic regression, and ophthalmoplegia/ptosis.