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Niemann-Pick Disease, Type C2

OMIM ID:

autosomal recessive

Niemann-Pick Disease, Type C2

Alternate Names

NPC2

Defective Genes

NPC2

Clinical Characteristics

Ocular Features

The primary ocular feature of type C2 Niemann-Pick disease is supranuclear gaze palsy.  A cherry red spot is rarely seen. 

Systemic Features

Neurodegeneration is the outstanding clinical manifestation and often the cause of death.  The onset usually occurs in infancy and the course is rapid with death often in the first year of life.  The clinical disease is similar to that of the more common type C1 (257220) although there is considerable clinical heterogeneity in all types of NPC.  Pulmonary involvement can be a prominent feature of C2 disease.  Other neurologic symptoms include ataxia, facial dyskinesis, bradykinesia, expressive aphasia, dysarthria and cognitive decline.  Visceromegaly seems to be less common than in type C1 (257220).  Cholesterol esterification is impaired with accumulation in intracellular organelles. 

Genetics

Inheritance

Like other types of NPC disease, this disorder follows an autosomal recessive pattern of inheritance.  It results from mutations in the NPC2 gene (14q24.3).  These mutations are far less common than those in the NPC1 (257220)gene.  

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

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Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

Treatment is available for symptoms such as seizures and dystonia.  Good pulmonary hygiene is important and precautions should be taken to prevent aspiration. 

Selected Resources

Publications

Displaying 1 - 2 of 2

Niemann–Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2

PubMedID: 17470133

Niemann–Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2

PubMedID: 17470133