Niemann-Pick Disease
𧬠Niemann-Pick disease is a group of autosomal recessive lysosomal storage disorders. It results from either a deficiency of sphingomyelinase (Types A & B) or defective cholesterol trafficking (Type C). This leads to pathological accumulation of sphingomyelin and cholesterol in multiple organs.
π About
- Belongs to the family of sphingolipidoses.
- First described by Albert Niemann (1914) and Ludwig Pick (1927).
- Leads to hepatosplenomegaly, lung disease, and neurological decline depending on subtype.
- More common in Ashkenazi Jewish population (Types A & B).
𧬠Aetiology
- Type A & B: Mutations in SMPD1 gene β acid sphingomyelinase deficiency.
- Type C1/C2: Mutations in NPC1 (95%) or NPC2 (5%) β defective cholesterol and lipid transport in lysosomes.
- Inheritance: Autosomal recessive.
π Populations Affected
- π’ Ashkenazi Jews β NPA & NPB
- π’ French Canadian population of Nova Scotia β NPCD variant
- π’ Maghreb region (North Africa) β NPB
- π’ Spanish-American population (New Mexico/Colorado) β NPC
π Types & Clinical Features
- Type A (infantile, severe):
- Onset in infancy (by 3β6 months)
- Hepatosplenomegaly, failure to thrive, recurrent infections
- Neurological regression, cherry-red macular spot π
- Interstitial lung disease, respiratory failure
- Death typically by age 2β3
- Type B (chronic visceral):
- Onset in mid-childhood/adolescence
- Hepatosplenomegaly, cytopenias (anaemia, thrombocytopenia)
- Interstitial lung disease, short stature
- Neurological involvement usually absent
- Survival into adulthood possible
- Type C (neurological form):
- Childhood or adolescent onset
- Ataxia, dystonia, dysarthria, dysphagia
- Vertical supranuclear gaze palsy (VSGP) π β pathognomonic
- Progressive intellectual decline & seizures
- May also cause neonatal cholestatic jaundice or hepatosplenomegaly
π¬ Investigations
- Bloods: Pancytopenia (due to hypersplenism); deranged LFTs.
- Enzyme assay: Acid sphingomyelinase activity (Types A & B).
- Genetic testing: SMPD1, NPC1, NPC2 mutations (confirmatory; allows prenatal diagnosis).
- Bone marrow biopsy: Foam cells (lipid-laden macrophages).
- Neuroimaging: May show cerebral/cerebellar atrophy in Type C.
- Filipin staining: Detects abnormal cholesterol storage (Type C).
π©Ή Management
- Type A: Supportive/palliative care only (no cure).
- Type B: Symptomatic treatment:
- Transfusions for cytopenias
- Oxygen therapy for lung disease
- Consider liver or bone marrow transplantation in select cases
- Type C: Miglustat (substrate reduction therapy) can slow neurological progression.
- All types: Supportive care (seizure management, physiotherapy, respiratory care, genetic counselling).
π Prognosis
- Type A: Fatal by age 2β3.
- Type B: Variable; survival into adulthood with chronic morbidity.
- Type C: Progressive neurological decline, survival usually into adolescence or early adulthood.
π References