IEMbase 0163: GCDH-related glutaric acidemia type 1
Scope
| Field | Value |
|---|---|
| IEMbase ID | 163 |
| Nosology | 1.2.05.01 |
| Gene | GCDH |
| External IDs | OMIM:231670; ORPHA:25 |
| Generated mapping | MAPPED to Glutaryl-CoA_Dehydrogenase_Deficiency.yaml |
| Candidate DisMech targets | Glutaryl-CoA_Dehydrogenase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as GCDH-related glutaryl-CoA dehydrogenase deficiency, with alternate labels glutaric acidemia type 1 and GA-I. Treatability is marked yes.
The biochemical rows include blood and plasma C5-DC glutarylcarnitine reported as normal to increased, urinary 3-hydroxyglutaric acid normal to increased, glutaric acid in dried blood spot, plasma, and urine normal to increased, urinary glutaconic acid normal to increased, increased ASAT/ALAT and creatine kinase, and plasma glucose decreased to normal. The clinical rows include macrocephaly, temporal hypoplasia/dilated external CSF spaces, striatal atrophy, periventricular white-matter abnormalities, acute encephalopathic crises, dystonia, dyskinesia, chorea, parkinsonism, hypokinesia, movement disorder, axial hypotonia, ataxia, dysarthria, feeding/swallowing difficulties, vomiting, pneumonia, acrodermatitis, peripheral neuropathy, headache, vertigo, and gliomas. IEMbase treatment rows include carnitine, lysine restriction, protein-defined diet, and sick-day management.
DisMech phenotype coverage
Glutaryl-CoA_Dehydrogenase_Deficiency.yaml is the correct target. It models
biallelic GCDH loss of function, impaired lysine, hydroxylysine, and tryptophan
catabolism, accumulation of glutaric acid, 3-hydroxyglutaric acid, and
glutarylcarnitine, brain exposure to toxic catabolites, striatal vulnerability,
acute encephalopathic crises, dystonia, macrocephaly, frontotemporal atrophy,
white-matter changes, newborn screening, lysine-restricted diet, carnitine,
emergency illness management, and investigational gene therapy, chaperone, and
bezafibrate approaches.
Concordance and completeness
Judgement: correct mapping with high concordance.
The IEMbase and DisMech profiles agree on GCDH, GA1 identity, C5DC, glutaric/3-hydroxyglutaric acid biomarkers, macrocephaly, striatal injury, white-matter imaging, encephalopathic crises, dystonia/movement disorder, and standard metabolic treatment. DisMech is stronger for mechanistic causality, module-level treatment rationale, newborn screening, and investigational treatments. IEMbase adds or foregrounds glutaconic acid, ASAT/ALAT, creatine kinase, glucose, acrodermatitis, peripheral neuropathy, pneumonia, vertigo, abasia/astasia, and gliomas as review targets.
Curation actions
- Keep the mapping to
Glutaryl-CoA_Dehydrogenase_Deficiency.yaml. - Consider future biomarker refinement for glutaconic acid, ASAT/ALAT, creatine kinase, glucose, and the "normal to increased" low-excreter wording.
- Review the rarer IEMbase phenotype rows, especially gliomas, acrodermatitis, peripheral neuropathy, pneumonia, vertigo, abasia, and astasia.