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IEMbase 0298: SMPD1-related Acid sphingomyelinase deficiency

Scope

Field Value
IEMbase ID 298
Nosology 20.1.03.01
Gene SMPD1
External IDs OMIM:257200; OMIM:607616; ORPHA:77292
Generated mapping CANDIDATE; Niemann-Pick_Disease_Type_A.yaml
Candidate DisMech targets Niemann-Pick_Disease_Type_A.yaml; Niemann-Pick_Disease_Type_B.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents the acid sphingomyelinase deficiency spectrum and explicitly names Niemann-Pick type A as severe and type B as milder. Inheritance is autosomal recessive and treatability is unknown in the cached record.

The phenotype rows mix type A and type B features: cherry red spot, deafness, foam cells, hepatosplenomegaly, hypoxia, liver cirrhosis, lymphadenopathy, pancytopenia, pulmonary interstitial changes, thrombocytopenia, vision loss or optic atrophy, developmental delay, failure to thrive, feeding difficulties, hypotonia, jaundice, and seizures. Biochemical rows show increased serum lysosphingomyelin and decreased sphingomyelinase activity, with the greatest enzyme reduction in neonatal rows.

DisMech phenotype coverage

The generated type A candidate is biologically valid but incomplete for the IEMbase label. Local DisMech has separate entries for the main SMPD1 spectrum ends: Niemann-Pick_Disease_Type_A.yaml and Niemann-Pick_Disease_Type_B.yaml.

The type A file covers profound SMPD1/acid sphingomyelinase deficiency, lysosomal sphingomyelin and secondary lipid accumulation, hepatosplenomegaly, failure to thrive, neurodegeneration, hypotonia, developmental regression, and cherry red spot. The type B file covers residual enzyme activity, visceral and pulmonary sphingomyelin storage, hepatosplenomegaly, thrombocytopenia, interstitial lung disease, atherogenic dyslipidemia, short stature, delayed puberty, osteopenia, and olipudase alfa enzyme replacement.

Concordance and completeness

Judgement: split the IEMbase spectrum record across local type A and type B coverage; do not treat the generated type A candidate as complete.

IEMbase and DisMech agree on SMPD1 causality, recessive inheritance, acid sphingomyelinase deficiency, lysosomal sphingomyelin storage, foam-cell visceral disease, hepatosplenomegaly, thrombocytopenia/cytopenias, pulmonary interstitial disease, neurologic severe-infantile disease, hypotonia, developmental delay/regression, cherry red spot, and failure to thrive.

DisMech is more precise because it keeps type A and type B as distinct local entities with different residual-enzyme, CNS, pulmonary, and treatment implications. IEMbase adds useful spectrum-level prompts for deafness, hypoxia, liver cirrhosis, lymphadenopathy, pancytopenia, vision loss/optic atrophy, feeding difficulty, jaundice, lysosphingomyelin, and age-stratified enzyme severity.

Curation actions

  • Resolve this record as spectrum-level coverage spanning Niemann-Pick_Disease_Type_A.yaml and Niemann-Pick_Disease_Type_B.yaml.
  • Avoid importing type B pulmonary/visceral rows into the type A file without subtype context, and avoid importing severe neurologic type A rows into type B.
  • Review lysosphingomyelin and the IEMbase type-specific clinical rows for possible addition to the appropriate local subtype files.