Transketolase Deficiency

Mendelian MONDO:0014881 Pathograph 7 Show in embeddings browser Inborn disorder of pentose phosphate metabolism Inborn Error of Metabolism

Transketolase deficiency is an ultra-rare autosomal recessive inborn error of the non-oxidative branch of the pentose phosphate pathway caused by biallelic pathogenic variants in TKT. Transketolase is a thiamine-dependent enzyme that reversibly transfers two-carbon units between sugar phosphates, linking the pentose phosphate pathway to glycolysis and recycling pentose phosphates. Loss of transketolase activity blocks non-oxidative pentose-phosphate metabolism, producing characteristic accumulation of the polyols erythritol, arabitol, and ribitol together with pentose(-ulose) phosphates in urine and plasma, and is thought to reduce NADPH availability for reductive biosynthesis and glutathione-dependent redox defense. Affected individuals present with short stature and developmental delay, frequently with congenital heart defects; chronic diarrhea and cataracts have been reported in older individuals. The disorder was first defined in three families (five affected individuals) by whole-exome sequencing, with enzymatic and urinary-metabolite confirmation. Management is largely supportive.

Ask OpenScientist

Ask a research question about Transketolase Deficiency. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

1
Mappings
1
Inheritance
3
Pathophys.
6
Phenotypes
1
Hypotheses
7
Pathograph
1
Genes
1
Medical Actions
🔗

Mappings

MONDO
MONDO:0014881 transketolase deficiency
skos:exactMatch MONDO OMIM:617044 / Orphanet:488618 cross-reference
MONDO:0014881 lists OMIM:617044 and Orphanet:488618 as exact cross-references and TKT as the associated gene.
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Transketolase deficiency is inherited in an autosomal recessive pattern; affected individuals carry biallelic TKT variants.
Autosomal recessive inheritance
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21"
The defining study establishes autosomal recessive inheritance of TKT deficiency.
◈

Mechanistic Hypotheses

1
Canonical TKT Non-Oxidative PPP / NADPH Redox Model
canonical_tkt_ppp_nadph_model CANONICAL
Evidence balance 2 support
Biallelic TKT variants reduce transketolase activity in the non-oxidative branch of the pentose phosphate pathway. The resulting block causes accumulation of polyols (erythritol, arabitol, ribitol) and pentose(-ulose) phosphates and is proposed to reduce NADPH available for nucleic acid synthesis, cell division, and maintenance of cerebral glutathione, thereby explaining growth failure (short stature) and neurodevelopmental delay.
Show evidence (2 references)
PMID:27259054 SUPPORT Human Clinical
"Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth."
The defining study proposes the NADPH-depletion mechanism linking the enzyme block to growth failure.
PMID:27259054 SUPPORT Human Clinical
"NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays."
The study links reduced NADPH to glutathione-dependent redox defense in the brain and neurodevelopmental delay.
⚙

Pathophysiology

3
Transketolase activity deficiency
Biallelic TKT variants reduce transketolase enzymatic activity. Enzymatic testing in affected individuals confirmed significantly reduced transketolase activity, establishing the primary catalytic defect in the non-oxidative branch of the pentose phosphate pathway.
TKT hgnc:11834 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves TKT (hgnc:11834). hgnc:11834 is a gene from the HUGO Gene Nomenclature Committee.
non-oxidative pentose phosphate pathway GO:0009052 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased non-oxidative pentose phosphate pathway, annotated with pentose-phosphate shunt, non-oxidative branch (GO:0009052). GO:0009052 is a biological process from the Gene Ontology. ↓ DECREASED
transketolase activity GO:0004802 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased transketolase activity (GO:0004802). GO:0004802 is a molecular function from the Gene Ontology. ↓ DECREASED
Downstream
Polyol and pentose-phosphate accumulation Reduced transketolase activity blocks recycling of pentose phosphates, causing accumulation of polyols and pentose(-ulose) phosphates.
Reduced NADPH-dependent biosynthesis and redox defense Transketolase deficiency is proposed to reduce NADPH synthesis, limiting reductive biosynthesis and maintenance of cerebral glutathione.
Show evidence (2 references)
PMID:27259054 SUPPORT Human Clinical
"Enzymatic testing confirmed significantly reduced transketolase activity."
Direct enzymatic confirmation of reduced transketolase activity in affected individuals.
PMID:27259054 SUPPORT Human Clinical
"Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate pathway."
Frames the enzyme defect within the non-oxidative branch of the pentose phosphate pathway.
Polyol and pentose-phosphate accumulation
Loss of transketolase activity leads to accumulation of the polyols erythritol, arabitol, and ribitol together with pentose(-ulose) phosphates, detectable in urine and plasma and diagnostic of the disorder.
non-oxidative pentose phosphate pathway GO:0009052 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal non-oxidative pentose phosphate pathway, annotated with pentose-phosphate shunt, non-oxidative branch (GO:0009052). GO:0009052 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Aciduria Accumulated polyols and pentose(-ulose) phosphates are excreted, producing an abnormal urinary metabolite (polyol/sugar-phosphate) profile.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"as well as elevated amounts of erythritol, arabitol, and ribitol in the plasma of affected individuals"
Documents plasma polyol elevations reflecting the metabolic block.
Reduced NADPH-dependent biosynthesis and redox defense
Reduced flux through the pentose phosphate pathway is proposed to lower NADPH availability, impairing nucleic acid synthesis and cell division (contributing to growth failure) and glutathione-dependent redox defense in the brain (contributing to neurodevelopmental delay).
glutathione metabolic process GO:0006749 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased glutathione metabolic process (GO:0006749). GO:0006749 is a biological process from the Gene Ontology. ↓ DECREASED ribose phosphate biosynthetic process GO:0046390 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased ribose phosphate biosynthetic process (GO:0046390). GO:0046390 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Short stature Impaired NADPH-dependent nucleic acid synthesis and cell division is proposed to underlie growth failure.
Global developmental delay Reduced NADPH-dependent maintenance of cerebral glutathione is proposed to contribute to neurodevelopmental delay.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth."
Links reduced NADPH to impaired nucleic acid synthesis, cell division, and growth failure.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Transketolase Deficiency Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Cardiovascular 1
Congenital heart defect VERY_FREQUENT Abnormal heart morphology HP:0001627 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Congenital heart defect, annotated with Abnormal heart morphology (HP:0001627). HP:0001627 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"Congenital heart defects were noted in four of the five affected individuals"
Congenital heart defects were present in 4 of 5 affected individuals.
Digestive 1
Chronic diarrhea HP:0002028 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic diarrhea (HP:0002028). HP:0002028 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion"
Chronic diarrhea was reported in the older affected individuals with the homozygous insertion.
Eye 1
Cataract HP:0000518 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cataract (HP:0000518). HP:0000518 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion"
Cataracts were reported in the older affected individuals with the homozygous insertion.
Genitourinary 1
Aciduria HP:0012072 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated urinary polyols and pentose phosphates, annotated with Aciduria (HP:0012072). HP:0012072 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected"
The abnormal urinary polyol/pentose-phosphate excretion is the diagnostic laboratory finding.
Nervous System 1
Global developmental delay VERY_FREQUENT HP:0001263 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Global developmental delay (HP:0001263). HP:0001263 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"All affected individuals had short stature and were developmentally delayed."
All five affected individuals were developmentally delayed (5/5), supporting a very frequent phenotype.
Growth 1
Short stature VERY_FREQUENT HP:0004322 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Short stature (HP:0004322). HP:0004322 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"All affected individuals had short stature and were developmentally delayed."
All five affected individuals had short stature (5/5), supporting a very frequent phenotype.
🧬

Genetic Associations

1
Biallelic TKT pathogenic variants (Causative)
Gene: TKT hgnc:11834 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is TKT (hgnc:11834). hgnc:11834 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE
Autosomal recessive inheritance
Show evidence (2 references)
PMID:27259054 SUPPORT Human Clinical
"Two families of Ashkenazi Jewish ancestry were homozygous for an 18 base pair in-frame insertion in TKT."
Documents a recurrent homozygous TKT insertion variant in affected families.
PMID:27259054 SUPPORT Human Clinical
"The third family was compound heterozygous for nonsense and missense variants in TKT."
Documents compound heterozygous TKT variants, supporting biallelic recessive causation.
💊

Medical Actions

1
Supportive care
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
No disease-specific therapy is established for transketolase deficiency; management is largely supportive, addressing growth, developmental, and cardiac manifestations. Reported clinical follow-up of affected individuals reflects symptomatic and supportive management.
📊

Prevalence

1
Worldwide
Cases In Literature Ultra Rare
The disorder was defined in three families with a total of five affected individuals; only a small number of cases are reported. Orphanet classifies it (ORPHA:488618) among ultra-rare disorders.
Show evidence (1 reference)
PMID:27259054 SUPPORT Human Clinical
"Our series includes three families with a total of five affected individuals, ranging in age from 4 to 25 years."
The report documents the small number of affected individuals in the literature.
{ }

Source YAML

click to show 
name: Transketolase Deficiency
creation_date: "2026-07-07T00:00:00Z"
category: Mendelian
synonyms:
- TKT deficiency
- Short stature-developmental delay-congenital heart defect syndrome
- SDDHD
description: >
  Transketolase deficiency is an ultra-rare autosomal recessive inborn error of
  the non-oxidative branch of the pentose phosphate pathway caused by biallelic
  pathogenic variants in TKT. Transketolase is a thiamine-dependent enzyme that
  reversibly transfers two-carbon units between sugar phosphates, linking the
  pentose phosphate pathway to glycolysis and recycling pentose phosphates.
  Loss of transketolase activity blocks non-oxidative pentose-phosphate
  metabolism, producing characteristic accumulation of the polyols erythritol,
  arabitol, and ribitol together with pentose(-ulose) phosphates in urine and
  plasma, and is thought to reduce NADPH availability for reductive
  biosynthesis and glutathione-dependent redox defense. Affected individuals
  present with short stature and developmental delay, frequently with
  congenital heart defects; chronic diarrhea and cataracts have been reported
  in older individuals. The disorder was first defined in three families
  (five affected individuals) by whole-exome sequencing, with enzymatic and
  urinary-metabolite confirmation. Management is largely supportive.
disease_term:
  preferred_term: transketolase deficiency
  term:
    id: MONDO:0014881
    label: transketolase deficiency
parents:
- Inborn disorder of pentose phosphate metabolism
- Inborn Error of Metabolism
notes: >-
  MONDO:0014881 (transketolase deficiency) cross-references OMIM:617044 and
  Orphanet:488618 and records TKT (HGNC:11834) as the associated gene, matching
  the IEMbase WP-008 seed row 3.5.04.01. The Orphanet synonym
  "short stature-developmental delay-congenital heart defect syndrome"
  (SDDHD) reflects the core clinical triad. NEC preflight (gene TKT, OMIM
  617044, ORPHA 488618) confirmed against the MONDO record before curation.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0014881
      label: transketolase deficiency
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO OMIM:617044 / Orphanet:488618 cross-reference
    mapping_justification: >-
      MONDO:0014881 lists OMIM:617044 and Orphanet:488618 as exact
      cross-references and TKT as the associated gene.
inheritance:
- name: Autosomal recessive inheritance
  description: >
    Transketolase deficiency is inherited in an autosomal recessive pattern;
    affected individuals carry biallelic TKT variants.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21"
    explanation: The defining study establishes autosomal recessive inheritance of TKT deficiency.
prevalence:
- population: Worldwide
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    The disorder was defined in three families with a total of five affected
    individuals; only a small number of cases are reported. Orphanet classifies
    it (ORPHA:488618) among ultra-rare disorders.
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our series includes three families with a total of five affected individuals, ranging in age from 4 to 25 years."
    explanation: The report documents the small number of affected individuals in the literature.
mechanistic_hypotheses:
- hypothesis_group_id: canonical_tkt_ppp_nadph_model
  hypothesis_label: Canonical TKT Non-Oxidative PPP / NADPH Redox Model
  status: CANONICAL
  description: >
    Biallelic TKT variants reduce transketolase activity in the non-oxidative
    branch of the pentose phosphate pathway. The resulting block causes
    accumulation of polyols (erythritol, arabitol, ribitol) and
    pentose(-ulose) phosphates and is proposed to reduce NADPH available for
    nucleic acid synthesis, cell division, and maintenance of cerebral
    glutathione, thereby explaining growth failure (short stature) and
    neurodevelopmental delay.
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth."
    explanation: The defining study proposes the NADPH-depletion mechanism linking the enzyme block to growth failure.
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays."
    explanation: The study links reduced NADPH to glutathione-dependent redox defense in the brain and neurodevelopmental delay.
genetic:
- name: Biallelic TKT pathogenic variants
  gene_term:
    preferred_term: TKT
    term:
      id: hgnc:11834
      label: TKT
  association: Causative
  relationship_type: CAUSATIVE
  features: >
    Transketolase deficiency is caused by biallelic pathogenic variants in TKT.
    Reported variants include an 18-base-pair in-frame insertion (homozygous in
    two Ashkenazi Jewish families) and compound heterozygous nonsense and
    missense variants.
  inheritance:
  - name: Autosomal recessive inheritance
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Two families of Ashkenazi Jewish ancestry were homozygous for an 18 base pair in-frame insertion in TKT."
    explanation: Documents a recurrent homozygous TKT insertion variant in affected families.
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The third family was compound heterozygous for nonsense and missense variants in TKT."
    explanation: Documents compound heterozygous TKT variants, supporting biallelic recessive causation.
pathophysiology:
- name: Transketolase activity deficiency
  description: >
    Biallelic TKT variants reduce transketolase enzymatic activity. Enzymatic
    testing in affected individuals confirmed significantly reduced
    transketolase activity, establishing the primary catalytic defect in the
    non-oxidative branch of the pentose phosphate pathway.
  genes:
  - preferred_term: TKT
    term:
      id: hgnc:11834
      label: TKT
  molecular_functions:
  - preferred_term: transketolase activity
    modifier: DECREASED
    term:
      id: GO:0004802
      label: transketolase activity
  biological_processes:
  - preferred_term: non-oxidative pentose phosphate pathway
    modifier: DECREASED
    term:
      id: GO:0009052
      label: pentose-phosphate shunt, non-oxidative branch
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Enzymatic testing confirmed significantly reduced transketolase activity."
    explanation: Direct enzymatic confirmation of reduced transketolase activity in affected individuals.
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate pathway."
    explanation: Frames the enzyme defect within the non-oxidative branch of the pentose phosphate pathway.
  downstream:
  - target: Polyol and pentose-phosphate accumulation
    description: >
      Reduced transketolase activity blocks recycling of pentose phosphates,
      causing accumulation of polyols and pentose(-ulose) phosphates.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:27259054
      reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected"
      explanation: Diagnostic urinary metabolite profile directly reflects the non-oxidative PPP block.
  - target: Reduced NADPH-dependent biosynthesis and redox defense
    description: >
      Transketolase deficiency is proposed to reduce NADPH synthesis, limiting
      reductive biosynthesis and maintenance of cerebral glutathione.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Diminished NADPH generation limiting glutathione-dependent redox defense.
    evidence:
    - reference: PMID:27259054
      reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays."
      explanation: Links the metabolic block to NADPH/glutathione redox defense in the brain.
- name: Polyol and pentose-phosphate accumulation
  description: >
    Loss of transketolase activity leads to accumulation of the polyols
    erythritol, arabitol, and ribitol together with pentose(-ulose)
    phosphates, detectable in urine and plasma and diagnostic of the disorder.
  biological_processes:
  - preferred_term: non-oxidative pentose phosphate pathway
    modifier: ABNORMAL
    term:
      id: GO:0009052
      label: pentose-phosphate shunt, non-oxidative branch
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "as well as elevated amounts of erythritol, arabitol, and ribitol in the plasma of affected individuals"
    explanation: Documents plasma polyol elevations reflecting the metabolic block.
  downstream:
  - target: Aciduria
    description: >
      Accumulated polyols and pentose(-ulose) phosphates are excreted, producing
      an abnormal urinary metabolite (polyol/sugar-phosphate) profile.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:27259054
      reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected"
      explanation: The diagnostic urinary polyol/pentose-phosphate excretion is the biochemical endpoint.
- name: Reduced NADPH-dependent biosynthesis and redox defense
  description: >
    Reduced flux through the pentose phosphate pathway is proposed to lower
    NADPH availability, impairing nucleic acid synthesis and cell division
    (contributing to growth failure) and glutathione-dependent redox defense
    in the brain (contributing to neurodevelopmental delay).
  biological_processes:
  - preferred_term: glutathione metabolic process
    modifier: DECREASED
    term:
      id: GO:0006749
      label: glutathione metabolic process
  - preferred_term: ribose phosphate biosynthetic process
    modifier: DECREASED
    term:
      id: GO:0046390
      label: ribose phosphate biosynthetic process
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth."
    explanation: Links reduced NADPH to impaired nucleic acid synthesis, cell division, and growth failure.
  downstream:
  - target: Short stature
    description: >
      Impaired NADPH-dependent nucleic acid synthesis and cell division is
      proposed to underlie growth failure.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:27259054
      reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth."
      explanation: The defining study links the NADPH deficit to the growth phenotype.
  - target: Global developmental delay
    description: >
      Reduced NADPH-dependent maintenance of cerebral glutathione is proposed
      to contribute to neurodevelopmental delay.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:27259054
      reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays."
      explanation: The defining study links reduced cerebral glutathione to the neurodevelopmental phenotype.
phenotypes:
- name: Short stature
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Short stature
    term:
      id: HP:0004322
      label: Short stature
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All affected individuals had short stature and were developmentally delayed."
    explanation: All five affected individuals had short stature (5/5), supporting a very frequent phenotype.
- name: Global developmental delay
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All affected individuals had short stature and were developmentally delayed."
    explanation: All five affected individuals were developmentally delayed (5/5), supporting a very frequent phenotype.
- name: Congenital heart defect
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Congenital heart defect
    term:
      id: HP:0001627
      label: Abnormal heart morphology
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Congenital heart defects were noted in four of the five affected individuals"
    explanation: Congenital heart defects were present in 4 of 5 affected individuals.
- name: Cataract
  phenotype_term:
    preferred_term: Cataract
    term:
      id: HP:0000518
      label: Cataract
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion"
    explanation: Cataracts were reported in the older affected individuals with the homozygous insertion.
- name: Chronic diarrhea
  phenotype_term:
    preferred_term: Chronic diarrhea
    term:
      id: HP:0002028
      label: Chronic diarrhea
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion"
    explanation: Chronic diarrhea was reported in the older affected individuals with the homozygous insertion.
- category: Laboratory
  name: Aciduria
  description: >
    Affected individuals excrete elevated amounts of the polyols erythritol,
    arabitol, and ribitol together with pentose(-ulose)-5-phosphates in urine,
    the diagnostic biochemical signature of transketolase deficiency.
  phenotype_term:
    preferred_term: Elevated urinary polyols and pentose phosphates
    term:
      id: HP:0012072
      label: Aciduria
  evidence:
  - reference: PMID:27259054
    reference_title: "Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected"
    explanation: The abnormal urinary polyol/pentose-phosphate excretion is the diagnostic laboratory finding.
treatments:
- name: Supportive care
  description: >
    No disease-specific therapy is established for transketolase deficiency;
    management is largely supportive, addressing growth, developmental, and
    cardiac manifestations. Reported clinical follow-up of affected individuals
    reflects symptomatic and supportive management.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care