IEMbase 0115: ALAD-related delta-aminolevulinate dehydratase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 115 |
| Nosology | 17.1.03.01 |
| Gene | ALAD |
| External IDs | OMIM:125270; ORPHA:100924 |
| Generated mapping | MAPPED, high confidence |
| Candidate DisMech targets | Porphyria_due_to_ALA_Dehydratase_Deficiency.yaml; secondary umbrella subtype in Inherited_Porphyria.yaml#Porphyria due to ALA Dehydratase Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as ALAD-related delta-aminolevulinate dehydratase deficiency, with alternate labels Doss porphyria, porphobilinogen synthase deficiency, and ALAD. Treatability is marked yes.
The characteristic biochemical rows are markedly decreased red-blood-cell delta-ALA dehydratase, increased urinary delta-ALA, and increased urinary coproporphyrin III. Clinical rows include coma, constipation, hyperesthesia, hypertension, motor neuropathy, nausea, renal failure, tachycardia, and vomiting. Treatments listed are heme arginate infusion and hydroxyurea.
DisMech phenotype coverage
Porphyria_due_to_ALA_Dehydratase_Deficiency.yaml is the correct canonical
target. It models biallelic ALAD pathogenic variants, reduced porphobilinogen
synthase activity, markedly reduced erythrocyte ALAD activity, upstream ALA
accumulation, urinary coproporphyrins, acute neurovisceral attacks, and the key
diagnostic distinction from AIP: little or no PBG overproduction.
The local treatment section directly covers hemin/heme arginate, glucose or carbohydrate loading, the uncertain status of givosiran in ADP, and hydroxyurea as an experimental erythroid-directed option.
Concordance and completeness
Judgement: correct standalone mapping with high biochemical concordance.
The overlap is strong for ALAD enzyme deficiency, urinary ALA, coproporphyrin abnormality, acute neurovisceral symptoms, and heme arginate. DisMech is richer for mechanism and for distinguishing inherited ADP from AIP and acquired ALAD inhibition. IEMbase adds a few clinical rows that could be surfaced more explicitly in the standalone entry, especially hyperesthesia, hypertension, tachycardia, renal failure, and coma.
Curation actions
- Keep
Porphyria_due_to_ALA_Dehydratase_Deficiency.yamlas the canonical target. - Keep the inherited porphyria umbrella subtype as secondary classification context.
- Review IEMbase's autonomic, renal, and severe encephalopathic rows for future ADP phenotype expansion.