IEMbase 0293: PSAP-related Metachromatic leukodystrophy-like disorder due to saposin B deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 293 |
| Nosology | 20.1.11.01 |
| Gene | PSAP |
| External IDs | OMIM:249900; ORPHA:309263 |
| Generated mapping | CANDIDATE; Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml |
| Candidate DisMech targets | Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml; partial context in Metachromatic_Leukodystrophy.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents isolated saposin B deficiency / cerebroside sulfatase activator deficiency, a PSAP-domain disorder producing a metachromatic-leukodystrophy-like phenotype. Inheritance is autosomal recessive and treatability is unknown.
The phenotype rows resemble MLD: ataxia, dysarthria, leukodystrophy, muscle weakness, neuropathy, seizures, slow nerve conduction velocity, spasticity, gait disturbance, irritability, emotional lability, psychotic behavior, and neurologic deterioration. Biochemical rows show increased CSF protein and markedly increased urinary sulfatide.
DisMech phenotype coverage
The generated saposin C candidate is not the correct target. Saposin C deficiency is a Gaucher-like glucosylceramide cofactor disorder, while this record is a saposin B sulfatide/MLD-like disorder.
Metachromatic_Leukodystrophy.yaml provides the closest local phenotype and
biochemical context. It covers leukodystrophy, peripheral demyelination, motor
and neurologic regression, seizures, sulfatide accumulation, and urinary
sulfatide excretion. The local biochemical section explicitly notes that
urinary sulfatide excretion can confirm MLD whether caused by ARSA defects or
saposin B.
However, the local MLD entry is genetically and mechanistically centered on ARSA. It does not yet model PSAP/saposin B as a causal gene or as an isolated activator-defect subtype/entry.
Concordance and completeness
Judgement: reject the generated saposin C candidate; treat as partial local MLD context plus a missing saposin B-specific target.
IEMbase and local MLD coverage agree on the leukodystrophy, peripheral nerve, spasticity, seizure, gait, behavioral, and urinary sulfatide signal. The critical discordance is the proximal mechanism: IEMbase is PSAP/saposin B, whereas the local entry primarily represents ARSA deficiency. That makes this a false-positive candidate to saposin C and a partial false negative for a saposin B-specific DisMech entity.
IEMbase adds a focused checklist for any future saposin B curation: PSAP gene causality, sulfatide excretion, elevated CSF protein, psychiatric/behavioral features, dysarthria, gait disturbance, and slow nerve conduction.
Curation actions
- Do not map this record to
Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml. - Use
Metachromatic_Leukodystrophy.yamlonly as partial phenotype/biochemical context until a saposin B-specific entry or subtype is curated. - Consider a future PSAP/saposin B MLD-like disorder entry that preserves the activator-defect distinction from ARSA-deficient MLD.