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Niemann-Pick disease type C2

Monday 3 April 2006

Autosomal recessive metabolic disease

Synopsis

- vertical supranuclear gaze palsy
- pulmonary involvement, severe
- respiratory failure
- hepatomegaly
- neonatal jaundice
- spleen
-  splenomegaly
- dysphagia
- hypotonia
- developmental delay
- dysarthria
- loss of speech
- mental deterioration
- dementia
- spasticity
- dystonia
- seizures
- cerebellar ataxia
- cataplexy
- neurofibrillary tangles
- behavioral/psychiatric manifestations
- poor school performance
- behavioral problems
- perseverative behavior
- psychosis

HEMATOLOGY

- lipid-laden macrophages (foam cells on bone marrow biopsy)
- ’sea-blue’ histiocytes

PRENATAL MANIFESTATIONS :
- fetal ascites

LABORATORY

- normal or mildly reduced sphingomyelinase activity
- low cholesterol esterification rates
- abnormal cholesterol homeostasis
- foam cells (lipid-laden macrophages) in visceral organs and CNS
- foam cells (lipid-laden macrophages) contain polymorphic cytoplasmic inclusions consisting of lamellar osmiophilic membranes on electron microscopy

MISCELLANEOUS

- highly variable phenotype and age of onset
- neurologic involvement may occur in the absence of visceral involvement
- early death from respiratory failure may occur

Eiology

- Niemann-Pick disease type C2 is caused by mutation in the NPC2 gene (601015)