IEMbase 0112: HMBS-related porphobilinogen deaminase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 112 |
| Nosology | 17.1.04.01 |
| Gene | HMBS |
| External IDs | OMIM:176000; ORPHA:79276 |
| Generated mapping | MAPPED, high confidence |
| Candidate DisMech targets | Acute_Intermittent_Porphyria.yaml; secondary umbrella subtype in Inherited_Porphyria.yaml#Acute Intermittent Porphyria |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as HMBS-related porphobilinogen deaminase deficiency, with alternate labels acute intermittent porphyria, hydroxymethylbilane synthase deficiency, and AIP. Treatability is marked yes.
The characteristic biochemical rows are markedly increased urinary delta-ALA, increased urinary porphobilinogen, and markedly increased total urinary porphyrins in adolescence and adulthood. Clinical rows include anxiety, aggressive or psychotic behavior, coma, constipation, depression, hepatopathy, hyperesthesia, hypertension, hepatocellular carcinoma or hepatoblastoma, motor neuropathy, nausea, renal failure, seizures, tachycardia, and vomiting. Hemin is listed as pharmacological treatment.
DisMech phenotype coverage
Acute_Intermittent_Porphyria.yaml is the correct canonical target. It models
HMBS/PBGD deficiency in hepatocytes, triggered hepatic ALAS1 induction, and
hepatic ALA/PBG accumulation, with urinary and plasma ALA/PBG biochemical
markers. The local phenotype set covers abdominal pain, nausea/vomiting,
constipation, tachycardia, hypertension, peripheral neuropathy, muscle
weakness, tetraparesis, hyponatremia, seizure, psychosis, mental deterioration,
cranial nerve paralysis, and pain manifestations.
The local treatment section is richer than IEMbase: intravenous hemin, givosiran, prophylactic hemin, ovulation suppression, liver transplantation, and carbohydrate loading are all represented with mechanism links.
Concordance and completeness
Judgement: correct standalone mapping with high phenotype concordance.
The strongest overlap is acute hepatic precursor biochemistry, autonomic features, gastrointestinal attacks, neuropathy, seizure/psychosis, and hemin therapy. DisMech is much stronger for causal mechanism, plasma monitoring, and modern prophylactic/curative treatment options. IEMbase contributes a few review targets that are less explicit in the phenotype table, especially renal failure, hepatopathy, liver-cancer risk, hyperesthesia, coma, anxiety, and depression.
Curation actions
- Keep
Acute_Intermittent_Porphyria.yamlas the canonical target. - Treat the inherited porphyria umbrella subtype as secondary classification context, not the main target.
- Review whether chronic kidney disease/renal failure, liver-cancer risk, and broader neuropsychiatric rows should be added or surfaced more explicitly in the standalone AIP entry.