IEMbase 0220: PDHA1-related Pyruvate dehydrogenase E1 alpha deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 220 |
| Nosology | 5.1.01.01 |
| Gene | PDHA1 |
| External IDs | OMIM:312170 |
| Generated mapping | MAPPED; Pyruvate_Dehydrogenase_Deficiency.yaml |
| Candidate DisMech targets | Pyruvate_Dehydrogenase_Deficiency.yaml#E1-alpha deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as PDHA1-related pyruvate dehydrogenase E1 alpha deficiency, with alternate label PDH. The record is X-linked and treatability is marked yes.
The biochemical rows include increased alanine, lactate, lactate/pyruvate ratio, pyruvate, and ketones, with normal glucose. Characteristic clinical rows include corpus-callosum agenesis on MRI, dysmorphic features, failure to thrive, lactic acidosis, and microcephaly. Additional rows include developmental delay, drug-resistant epilepsy, hypotonia, Leigh syndrome, peripheral neuropathy, pyramidal signs, seizures, and multiple craniofacial features. Treatments listed by IEMbase are ketogenic diet and thiamine.
DisMech phenotype coverage
Pyruvate_Dehydrogenase_Deficiency.yaml is the correct target, with subtype
resolution to E1-alpha deficiency. The local entry covers PDHA1 as the most
common PDH deficiency gene, X-linked inheritance, reduced PDH complex activity,
blocked pyruvate decarboxylation to acetyl-CoA, lactate and pyruvate
accumulation, lactic acidosis, neurodevelopmental injury, hypotonia, seizures,
movement disorders, corpus-callosum abnormalities, microcephaly, dysmorphic
features, ketogenic diet, thiamine-responsive PDHA1 residual activity,
dichloroacetate, phenylbutyrate, biochemical testing, enzyme assay, molecular
testing, and brain MRI.
Concordance and completeness
Judgement: correct mapped target, with subtype resolution needed.
IEMbase and DisMech agree on PDHA1/E1-alpha identity, X-linked inheritance, the PDH biochemical block, lactate/pyruvate abnormalities, lactic acidosis, developmental delay, hypotonia, seizures/epilepsy, Leigh-spectrum CNS disease, corpus-callosum involvement, microcephaly, dysmorphism, ketogenic diet, and thiamine. IEMbase adds more granular craniofacial descriptors and flags drug-resistant epilepsy; DisMech is richer for mechanism, therapy nuance, and diagnostic workflow.
Curation actions
- Keep the record mapped to
Pyruvate_Dehydrogenase_Deficiency.yaml. - Prefer subtype resolution to
Pyruvate_Dehydrogenase_Deficiency.yaml#E1-alpha deficiency. - Consider reviewing IEMbase's granular facial-feature and drug-resistant epilepsy rows if the PDHA1 subtype is later enriched.