IEMbase 0136: ALDH6A1-related Methylmalonate semialdehyde dehydrogenase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 136 |
| Nosology | 1.2.17.01 |
| Gene | ALDH6A1 |
| External IDs | OMIM:603178; ORPHA:289307 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | No valid ALDH6A1/MMSDH target found; generated SSADH candidate is false |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as ALDH6A1-related methylmalonate semialdehyde dehydrogenase deficiency, abbreviated MMSDH. Treatability is marked unknown.
Characteristic biochemical rows include normal-to-increased urinary 2-aminoisobutyric acid, 3-aminoisobutyric acid, 3-hydroxyisobutyric acid, and ethylmalonic acid. Other rows include normal-to-increased methionine, beta-alanine, 3-hydroxypropionic acid, lactate, and decreased fibroblast methylmalonic semialdehyde dehydrogenase activity. Clinical rows include developmental delay, hepatomegaly, episodic vomiting, and failure to thrive.
DisMech phenotype coverage
No local standalone ALDH6A1/MMSDH entry was found. The generated
Succinic_Semialdehyde_Dehydrogenase_Deficiency.yaml candidate is a false
semialdehyde-dehydrogenase neighbor: SSADH deficiency is an ALDH5A1 disorder of
GABA catabolism with GABA/GHB accumulation, not ALDH6A1 methylmalonate
semialdehyde metabolism.
HIBCH deficiency and other valine-catabolism entries are pathway neighbors but do not cover ALDH6A1 disease scope.
Concordance and completeness
Judgement: true unmapped local disease gap.
The IEMbase record has a recognizable MMSDH biochemical pattern involving aminoisobutyric acids, 3-hydroxyisobutyric acid, ethylmalonic acid, and reduced MMSDH enzyme activity. Current DisMech captures adjacent valine or GABA pathway disorders, but not the ALDH6A1 disease entity.
Curation actions
- Keep this record unmapped.
- Reject the SSADH/ALDH5A1 candidate.
- Future curation should add ALDH6A1/MMSDH deficiency with the urinary organic acid and aminoisobutyric acid profile, failure to thrive, developmental delay, hepatomegaly, vomiting, and valine/thymine-catabolism mechanism.