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)