Definition
- Autosomal recessive lysosomal storage disorders with lipid accumulation in reticuloendothelial cells
Aetiology
- Types A and B result from acid sphingomyelinase deficiency (SMPD1)
- Type C results from NPC1 or NPC2 defects of cholesterol trafficking, without sphingomyelinase deficiency
Pathology
- Sphingomyelin accumulates in liver, spleen and brain
- Marrow infiltration with foam cells
Clinical Features
- Type A is infantile neurovisceral with death in early childhood
- Type B is chronic visceral with survival into adulthood
- Hepatosplenomegaly
- Pulmonary infiltrates
- Macular cherry red spot
- Spasticity and deafness
- Type C causes ataxia, dystonia and vertical supranuclear gaze palsy
- Delayed bone age
- Osteoporosis and fragility fractures
- Metaphyseal splaying with Erlenmeyer flask deformity
- Long vertebral pedicles
- Coxa valga
Investigations
- Acid sphingomyelinase enzyme assay in leucocytes
- Genetic testing
- Bone marrow shows foam cells
Differential Diagnosis
- Gaucher disease
- Other storage disorders with hepatosplenomegaly
Management
- Olipudase alfa enzyme replacement for non neurological manifestations of acid sphingomyelinase deficiency
- Miglustat for neurological symptoms of type C
- Bisphosphonates and fracture prevention
- Anaesthetic review for lung disease and thrombocytopenia
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.