Niemann-Pick disease (NPC) is a slow-progressing disorder in which the primary hallmark is accumulation of lipids in lysosomes. Symptoms are age dependent. Clinical signs during infancy are limited to the viscera, with hepatosplenomegaly, jaundice, and (in some instances) pulmonary infiltrates. Beyond late infancy, neurological symptoms begin to manifest. Classic presentation occurs in mid-to-late childhood with onset of ataxia, vertical supranuclear gaze palsy, and dementia. Dystonia and seizures are common features. Adults are likely to present with dementia or psychiatric symptoms.

NPC is inherited in an autosomal recessive manner. It is caused by mutations in either the NPC1 (in 95% of cases) or NPC2 (in 5% of the cases) genes. Most NPC1 cases involve compound heterozygotes of single-nucleotide variants. So far, over 511 variants have been described in NPC1 that cause Niemann Pick disease type C, and over 27 different variants in NPC2.

Niemann-Pick Disease Types

Type A: Hepatosplenomegaly (Enlarged liver and spleen), failure to thrive, psychomotor regression, interstitial lung disease eventually leading to respiratory failure, eye abnormality – cherry-red spot, generally do not survive past early childhood.

Type B: presents in mid-childhood, hepatosplenomegaly, recurrent lung infections, thrombocytopenia (low number of platelets), short stature, slowed bone mineralization, cherry-red spot in one-third of cases, neurological impairment, usually survive into adulthood.

Type C1 and C2 – become apparent in childhood, ataxia, inability to move eyes vertically (gaze palsy), dystonia (poor muscle tone), severe liver disease, interstitial lung disease, often cases decline in intellectual function, problems with speech and swallowing, one-third cases seizures, may survive into adulthood.

Niemann-Pick Disease Test & Therapy

Biochemical test: Acidic sphingomyelinase (Type A & B)
Biomarker test: Lyso-Sphingomyelin-509 & Lyso-Sphingomyelin-465 (Type A, B & C).
Gene: SMPD1 (A & B), NPC1/NPC2 (Type C)

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