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IEMbase 0108: ALAS2-related erythroid 5-aminolevulinate synthase superactivity

Scope

Field Value
IEMbase ID 108
Nosology 17.1.02.01
Gene ALAS2
External IDs OMIM:300752
Generated mapping UNMAPPED
Candidate DisMech targets Inherited_Porphyria.yaml#Erythropoietic Protoporphyria as current umbrella/subtype context
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as ALAS2-related erythroid 5-aminolevulinate synthase superactivity, with alternate label X-linked protoporphyria (XLDPP). Treatability is marked yes.

The biochemical rows are increased erythrocyte delta-ALA synthase activity, normal urinary total porphyrins, markedly increased erythrocyte protoporphyrin IX, and increased erythrocyte zinc protoporphyrin IX. The cached JSON has no clinical rows.

Treatment is pyridoxine.

DisMech phenotype coverage

The generated UNMAPPED status is a false negative for current local coverage. DisMech does not have a standalone X-linked protoporphyria entry, but Inherited_Porphyria.yaml explicitly models ALAS2-related X-linked protoporphyria in the erythropoietic protoporphyria/protoporphyria branch. The entry includes X-linked inheritance, increased ALAS2 activity, protoporphyrin IX accumulation, severe cutaneous phototoxicity, liver-risk context, increased erythrocyte or plasma protoporphyrin, and afamelanotide pharmacotherapy.

The existing subtype anchor is Inherited_Porphyria.yaml#Erythropoietic Protoporphyria, whose description includes FECH-related or ALAS2-related protoporphyria rather than splitting XLP as a separate subtype.

Concordance and completeness

Judgement: false negative to local umbrella/subtype coverage, with a future split decision needed.

DisMech is richer for clinical phototoxicity, mechanism, and group-level treatment context. IEMbase is richer for the XLP-specific diagnostic lab pattern: erythrocyte ALAS2 activity, normal urine porphyrins, erythrocyte PPIX, and zinc protoporphyrin IX. The treatment rows differ: IEMbase lists pyridoxine, while DisMech currently emphasizes afamelanotide for EPP/XLP light tolerance.

Curation actions

  • Resolve to Inherited_Porphyria.yaml#Erythropoietic Protoporphyria for now, noting that this is subtype-context coverage rather than a standalone XLP disease file.
  • Consider adding a distinct X-linked protoporphyria subtype or standalone entry if porphyria curation moves below umbrella level.
  • Review pyridoxine and XLP-specific biomarker rows before adding them locally.