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IEMbase 0294: PSAP-related Gaucher disease-like disorder due to saposin C deficiency

Scope

Field Value
IEMbase ID 294
Nosology 20.1.02.01
Gene PSAP
External IDs OMIM:610539; ORPHA:309263
Generated mapping MAPPED; Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml
Candidate DisMech targets Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents isolated saposin C deficiency, a PSAP cofactor disorder with a Gaucher-like presentation. Inheritance is autosomal recessive and treatability is unknown.

Clinical rows include anemia, abnormal eye movements, foam cells, hepatosplenomegaly, pathological fractures, myoclonic seizures, thrombocytopenia, bone pain, and developmental delay. Biochemical rows are particularly useful: markedly increased plasma chitotriosidase, normal beta-D-glucosidase activity, and increased serum glucosylsphingosine.

DisMech phenotype coverage

Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml is the correct local target. The local entry explicitly models PSAP variants abolishing saposin C, impaired glucocerebrosidase access to glucosylceramide despite normal GBA1 enzyme activity, lysosomal glucosylceramide accumulation, Gaucher-like macrophage storage, hepatosplenomegaly, and thrombocytopenia.

Local diagnosis also captures the main differentiator from classic Gaucher disease: a Gaucher-like phenotype with normal glucocerebrosidase activity and confirmatory PSAP sequencing.

Concordance and completeness

Judgement: correct high-concordance mapping to Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml.

IEMbase and DisMech agree on PSAP/saposin C identity, recessive inheritance, Gaucher-like macrophage storage, hepatosplenomegaly, thrombocytopenia, normal glucocerebrosidase activity, and increased glucosylsphingosine. DisMech is stronger for the cofactor-defect mechanism and for distinguishing saposin C deficiency from GBA1 Gaucher disease.

IEMbase adds phenotype prompts that are not all explicit locally: anemia, abnormal eye movements, foam cells, pathological fractures, myoclonic seizures, bone pain, developmental delay, and chitotriosidase. These should be reviewed carefully because the local entry is intentionally conservative and the published case base is small.

Curation actions

  • Keep this record mapped to Gaucher_Disease_Due_To_Saposin_C_Deficiency.yaml.
  • Consider adding normal beta-D-glucosidase plus elevated glucosylsphingosine and chitotriosidase as biochemical prompts if supported by the local evidence base.
  • Review IEMbase-only neurologic, ocular-motor, skeletal, hematologic, and foam cell rows before importing.