Niemann-Pick disease (NPD) is a group of rare metabolic disorders in which harmful quantities of a fatty substance (lipids) accumulate in the spleen, liver, lungs, bone marrow, and brain. Symptoms may include lack of muscle coordination, brain degeneration, learning problems, loss of muscle tone, increased sensitivity to touch, spasticity, feeding and swallowing difficulties, slurred speech, and an enlarged liver and spleen. Inheritance is autosomal recessive. This rare disease affects many body systems and has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.
Type A
Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.
Type B
Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.
Type C
The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.
Etiology
Niemann-Pick disease is divided into four main types according to the altered (mutated) gene and the signs and symptoms:
- Type A, caused by mutations in the SMPD1 gene. It is the most severe form, occurs in early infancy and is seen primarily in Jewish families.
- Type B , caused by mutations in the SMPD1 gene. Usually occurs in children, and affects the liver, spleen and lungs (visceral form), but generally does not affect the brain.
- Type C1, caused by mutations in the NPC1 gene. May occur at any age and affect the brain and the viscera.
- Type C2, caused by homozygous mutation in the NPC2 gene. Similar to type C1, but more severe, and mostly affecting the lungs.
Some classify type A and B as “acid sphingomyelinase (ASM) deficiency. NP type D is now considered as type C (when affected people are from Nova Scotia, Canada); other rarer types have being described.
There is currently no effective treatment for type A. Bone marrow transplantation, enzyme replacement and gene therapies may be helpful for people with type B. A medication called Miglustat has been shown to stabilize certain neurological symptoms in people with type C. Currently other treatments are under clinical investigation.
For more information on Niemann-Pick disease, visit Genetic and Rare Diseases (GARD) Information Center.
To learn more about rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/
