IEMbase 0291: PSAP-related Combined saposin deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 291 |
| Nosology | 20.1.16.01 |
| Gene | PSAP |
| External IDs | OMIM:611721; ORPHA:309263 |
| Generated mapping | MAPPED; Combined_Saposin_Deficiency.yaml |
| Candidate DisMech targets | Combined_Saposin_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents combined saposin deficiency / prosaposin deficiency due to PSAP. The cached disease label contains a source typo in the word "combined." Inheritance is autosomal recessive and treatability is unknown.
The clinical rows are sparse: neonatal and infantile developmental delay, hyperkinesia, and hypotonia. Biochemical rows are more specific and show the multi-sphingolipid cofactor pattern: decreased fibroblast ceramidase activity, increased plasma chitotriosidase, decreased fibroblast galactosylceramidase activity, and decreased fibroblast glucosylceramidase activity.
DisMech phenotype coverage
Combined_Saposin_Deficiency.yaml is the correct local target. The local entry
models biallelic PSAP loss, abolition of prosaposin and saposins A-D, combined
multi-sphingolipid lysosomal accumulation, severe neonatal neurodegeneration,
hepatosplenomegaly, thrombocytopenia, and cerebral demyelination. It also
distinguishes combined PSAP deficiency from isolated saposin C and saposin B
deficiencies.
Local biochemical coverage includes combined saposin A/B/C/D deficiency, but does not enumerate the IEMbase secondary hydrolase assay pattern for ceramidase, galactosylceramidase, and glucosylceramidase activities.
Concordance and completeness
Judgement: correct mapping to Combined_Saposin_Deficiency.yaml.
IEMbase and DisMech agree on PSAP/prosaposin identity, recessive inheritance, loss of multiple saposin-dependent sphingolipid degradation functions, early neurodevelopmental disease, and hypotonia. DisMech is richer for the conceptual boundary between combined prosaposin deficiency and isolated saposin deficiencies, and for hepatosplenic, hematologic, demyelinating, and neurodegenerative consequences.
IEMbase adds useful assay-level prompts: low ceramidase, galactosylceramidase, and glucosylceramidase activities in fibroblasts, plus increased chitotriosidase. These look like downstream functional readouts of saposin cofactor loss rather than primary mutations in ASAH1, GALC, or GBA/GBA1, so they should be framed carefully if imported.
Curation actions
- Keep this record mapped to
Combined_Saposin_Deficiency.yaml. - Preserve the distinction between combined PSAP/prosaposin deficiency and isolated saposin A, B, C, or D disorders.
- Consider adding the IEMbase fibroblast hydrolase assays and chitotriosidase as downstream biochemical review prompts, not as separate causal-gene claims.