Niemann-Pick disease type B

Other Names: Niemann Pick disease type B

Niemann-Pick disease type B is an inherited condition involving lipid metabolism. People with this condition experience a build up of lipids in the spleen, liver, lungs, bone marrow, and brain.

Epidemiology

Niemann-Pick disease types A and B is estimated to affect 1 in 250,000 individuals. Niemann-Pick disease type A occurs more frequently among individuals of Ashkenazi (eastern and central European) Jewish descent than in the general population. The incidence within the Ashkenazi population is approximately 1 in 40,000 individuals.

Cause

Niemann-Pick disease type B is caused by changes (mutations or variants) in the SMPD1 gene. This gene provides instructions for producing an enzyme called acid sphingomyelinase. This enzyme is found in lysosomes, which are compartments within cells that break down and recycle different types of molecules. Acid sphingomyelinase is responsible for the conversion of a fat (lipid) called sphingomyelin into another type of lipid called ceramide.

Mutations in SMPD1 lead to a shortage of acid sphingomyelinase, which results in reduced break down of sphingomyelin, causing this fat to accumulate in cells. This fat buildup causes cells to malfunction and eventually die. Over time, cell loss impairs function of tissues and organs including the brain, lungs, spleen, and liver in people with Niemann-Pick disease types A and B.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

The age of onset and rate of disease progression varies greatly among people with Niemann-Pick disease type B (NPD type B), but survival into adulthood is common. Signs and symptoms usually begin in early childhood but sometimes do not appear until adulthood. Signs and symptoms may include:

• An enlarged liver and spleen (hepatosplenomegaly) - This is the most common first sign of the disease, and enlargement may be mild or profound. The spleen may become progressively overactive (hypersplenism), and rarely, liver failure requires liver transplantation.
• Lipid abnormalities - Triglycerides and LDL cholesterol are often elevated, while HDL cholesterol is often low. This may cause early coronary artery disease.
• Thrombocytopenia (low blood platelet count) and leukopenia (low white blood cell count) - These typically worsen over time.
• Gradual worsening of lung function - Some people do not have impaired lung function while others are oxygen-dependent and have severe activity restrictions.
• Growth restriction and delayed bone age, which can result in significant short stature in adulthood
• Bone and joint pain
• Osteopenia (low bone mass) or osteoporosis, which can lead to an increased risk for fractures
• Delayed onset of puberty (often by several years)
• Tiredness (fatigue)

A reddish-brown "halo" surrounding the macula in the eyes or a distinct cherry red spot identified on an eye exam.

People with NPD type B usually do not have neurologic symptoms. However, some people with a more severe variant have greater severity of the symptoms above, as well as neurologic features such as ataxia, gross motor delays, learning difficulties, intellectual disabilities, psychiatric disorders, and/or nystagmus. When present, it is uncommon for neurologic features to be progressive or severe.

Of note, NPD type B differs significantly from NPD type A (a more severe, early-onset form of NPD), in which symptoms appear in early infancy, development does not progress beyond the 12-month level, and survival beyond age three is uncommon.

Diagnosis

A blood or bone marrow test can be done to diagnose types A and B. The test can tell who has the disease, but does not show if you are a carrier. DNA tests can be done to diagnose carriers of types A and B.

Other tests might include:

• Bone marrow aspiration
• Liver biopsy (usually not needed)
• Slit-lamp eye exam
• Tests to check level of ASM

Treatment

Treatment is aimed at addressing the symptoms present in each individual. Bone marrow transplantation has been attempted in a few individuals. Researchers are working to develop additional options for treatment, including enzyme replacement and gene therapy.

NIH genetic and rare disease info

• NIH info on Niemann-Pick disease type B

Niemann-Pick disease type B is a rare disease.

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