Niemann-Pick Types A and B (NPA and NPB) are caused by a mutation in the SMPD1 gene, leading to a deficiency of the enzyme, acid sphingomyelinase (ASM), which is required to metabolize the lipid sphingomyelin. If ASM is absent or not functioning properly, sphingomyelin cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems. Niemann-Pick Type C (NPC) is caused by a mutation in the NPC1 or NPC2 gene on chromosome 18 located at 18q11-q12. Niemann Pick Type C patients are not able to metabolize cholesterol and other lipids properly within the cell. All forms of Niemann-Pick are inherited in an autosomal recessive manner.
- Types A and B affect approximately 1 in 40,000 in the Ashkenazi population
- Type C is very rare, represented by the 500 cases diagnosed worldwide
Type A Niemann-Pick disease begins during infancy and is characterized by:
- An enlarged liver and spleen (hepatosplenomegaly)
- Failure to thrive
- Progressive deterioration of the nervous system.
- Children affected by this condition generally do not survive past early childhood.
- Type A Niemann-Pick disease occurs more frequently among individuals of Ashkenazi Jewish descent
Type B disease may include signs of:
- Growth retardation
- Problems with lung function (including frequent lung infections)
- Blood abnormalities such as abnormal cholesterol and lipid levels
- Individuals affected by this type of Niemann-Pick disease usually survive into adulthood
- Type B Niemann-Pick disease occurs in all populations
Type C disease has a wide clinical spectrum and a variable age of onset. Classically, children with NPC demonstrate:
- Neurological dysfunction with cerebellar ataxia
- Vertical gaze palsy
- Motor impairment
- Dysphagia (difficulty in swallowing)
- Psychotic episodes
- Progressive dementia
- NPC is always fatal- the vast majority of children die before age 20
There is no standard treatment that has proven to be effective for everyone, however supportive care may include involvement of specialists in gastroenterology, nutrition, physical and/or occupational therapy. Standard medications used to treat seizures, cataplexy (sudden loss of muscle strength), dystonia (abnormal movements due to incessant muscle contractions) and spasticity can be used in NPC patients.