Niemann-Pick Disease, Type C2

Associated Genes

NPC2 Gene
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number


Mode of Inheritance

Autosomal recessive

Gene Map Locus



Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder in which excessive amounts of harmful lipids accumulate in the spleen, liver, lungs, bone marrow, and brain. This will result in many complications including hepatosplenomegaly, ascites, seizures, neurological problems, and/or respiratory failure. The disease can start at ages that range between the prenatal period and 50 years. The earlier the disease onset is, the more severe the symptoms are. About 20% of cases have the severe infantile form with neurological involvement before age two and delayed motor milestones as well as hypotonia. The classic form of the disease occurs mostly in childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Affected adults are more likely to have dementia or psychiatric problems.

Globally, the estimated incidence of NPC is calculated at 1/140,000 births. NPC is divided into two forms according to the causative gene (NPC1 and NPC2). Diagnosis of NPC is mainly based on demonstrating these anomalies in cultured fibroblasts (especially through the cytochemical "filipine test"). Prenatal diagnosis is also available via molecular or cellular biology. Cholesterol lowering agents can be used as supporting factors, but they have no effect on the neurological signs of the disease. Generally, there is no available treatment for NPC to date.

Molecular Genetics

NPC2 forms 5% only of all cases with NPC. The causative gene, NPC2, has five exons and a size of approximately 13.5 Kb. This gene encodes a protein that is responsible for binding and transporting cholesterol, however, the exact function of this protein is not fully known. Mutations in NPC2 gene that cause low levels of or absence of the protein will result in presenting the signs and symptoms of the disease.

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
607625.1Saudi Arabia Global developmental delay; Microcephaly...NM_006432.5:c.88G>AHomozygousAutosomal, RecessiveAlazami et al. 2015 No organomegaly; nor...

Other Reports


Millat et al. (2001) described three Algerian cases from two unrelated consanguineous families with different clinical presentation of Niemann-Pick disease type C2 (NPC2). One of the families had a male patient who presented with cholestatic icterus until four months of age. He had also pulmonary involvement, hepatosplenomegaly, severe motor development delay from age seven to nine months, growth retardation, increasing pulmonary fibrosis, oxygen deficiency, and respiratory failure. He died at age 19 months. The other two patients from the second family were sisters of ages 21 and 27 years. Both of them had an onset of neurological symptoms during late childhood, slow progression of the disease with long survival, and no prominent pulmonary involvement.

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