What Is Niemann-Pick Disease?

Niemann-Pick Disease Symptoms
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Niemann-Pick disease is a rare genetic medical condition. There are four variants of this disease, categorized as type A, type B, type C, and type D. Niemann-Pick disease causes a variety of medical problems, and it often advances rapidly. The symptoms and effects of all of the variants of Niemann-Pick disease result from the buildup of sphingomyelin, a type of fat, in the body. 

Unfortunately, there is no definitive cure for Niemann-Pick disease, and people who have the disease experience substantial illness and death at a young age. If you or your child has been diagnosed with Niemann-Pick disease, you can benefit by knowing as much about the condition as possible.

Causes

The cause of Niemann-Pick disease is relatively complicated. People who have this disease inherit one of several genetic defects, resulting in a buildup of sphingomyelin, a type of fat. As the sphingomyelin builds up in the cells of the liver, spleen, bones, or nervous system, these regions of the body cannot function as they should, resulting in any of the symptoms that are characteristic of the disease.

Types

The different types of Niemann-Pick disease differ from each other in several ways.

  • They are caused by different genetic defects.
  • They are each characterized by different biochemical processes that cause sphingomyelin to build up.
  • The excess sphingomyelin affects different parts of the body.
  • They each begin at different ages.
  • The outcome of each type is not the same.

What they all have in common is that they are all genetic defects that result in excessive sphingomyelin.

Niemann-Pick Type A

Type A begins to produce symptoms during infancy and is considered the most severe variant of Niemann-Pick disease. It is also one of the variants that involves the nervous system.

  • Symptoms: The symptoms begin around age six months and include: slow physical growth, weak muscles and weak muscle tone, trouble eating, breathing problems and slow or delayed development of cognitive abilities such as sitting up and speaking. Often, infants with Niemann-Pick type A develop normally or almost normally for the first few months of life and then begin to have symptoms. 
  • Diagnosis: If your child has not been developing normally, there can be a number of possible causes. Many children who have Niemann-Pick type A have a large spleen and a large liver, high cholesterol levels, and a cherry red appearing spot which is seen on examination of the eye. These signs do not confirm the diagnosis, however. If your doctor thinks that Niemann-Pick type A is the cause of your child’s symptoms, there are a few tests that confirm the disease. Acid Sphingomyelinase is expected to be decreased, and this level can be measured in the white blood cells. There is also a genetic test that can identify the gene abnormally.
  • Treatment: If your child has been diagnosed with Niemann-Pick type A, there are no treatments beyond support and comfort. Unfortunately, children with this disease are not expected to survive beyond age 3 or 4. 
  • Cause: Niemann-Pick type A is caused by an irregularity of a gene called the SMPD1 gene. This gene codes for production of sphingomyelinase, an enzyme that breaks down sphingomyelin, a fat that is normally present inside the cells of the body. When sphingomyelin cannot be broken down as it should, the cells in the body accumulate it, and the presence of this excess fat prevents the organs from functioning normally. 
  • Genetics: This disease is autosomal recessive, which means that a child must have received the gene from both parents in order for the illness to develop. People of Ashkenazi Jewish descent have a higher chance of inheriting this condition.

Niemann-Pick Type B

Type B is considered to be a milder form of Niemann-Pick disease than type A. It is caused by the same type of genetic abnormality, which results in sphingomyelinase deficiency. A big difference between type A and type B is that people who have type B are able to produce substantially more sphingomyelinase than people who have type A. This difference results in less sphingomyelin build up, which may at least partially account for the older age at which the type B disease begins, the better outcomes, and longer survival. It does not completely explain why type A, while neurological involvement is uncommon in type B. 

  • Symptoms: The symptoms begin during adulthood and can include a large liver, a large spleen, breathing difficulties, and bleeding. Older adults typically have a better outcome and longer survival than younger adults who have this disease variant. 
  • Diagnosis: As with type A, Acid Sphingomyelinase is decreased in the white blood cells, and the genetic test for SMPD1 can confirm the disease. Blood levels of cholesterol and triglycerides may be elevated. Some people who have Niemann-Pick type B may have a cherry red spot on examination of the eye. 
  • Treatment: There are several treatments for Niemann-Pick type B, but they do not cure the disease. These include blood and platelet transfusions and breathing assistance. Organ transplant may help prolong survival and reduce the effects of the disease, but it also is not a cure. 
  • Cause: Niemann-Pick type B is caused by a defect in the SMPD1 gene, which results in reduced production of Acid Sphingomyelinase, which causes sphingomyelin to build up in the cells, which in turn interferes with the function of several organs in the body. 
  • Genetics: All of the types of Niemann-Pick disease are autosomal recessive, including type B. Some populations are more likely to inherit Niemann-Pick type B, including those of Ashkenazi Jewish descent or those who are descended from some regions in North Africa.

Niemann-Pick Type C

Niemann-Pick type C is the most common variant of this disease, but it is still quite rare, with about 500 newly diagnosed people per year worldwide. 

  • Symptoms: The symptoms of Niemann-Pick type C can begin at any age, but generally start in early childhood. The symptoms include learning delay, muscle weakness and decreased coordination. These problems begin after the skills had already been developing normally for a few years. Children with Niemann-Pick type C may also lose the ability to look up and down with their eyes and can develop a yellowish skin color. Trouble speaking and walking may develop, along with clumsiness. Seizures and jerking muscles, as well as sudden loss of muscle tone in response to strong emotions are all the result of involvement of the brain. 
  • Diagnosis: Children and adults with Niemann-Pick type C can have an enlarged liver, and enlarged spleen, and lung disease. The diagnosis of Niemann-Pick type C depends on the clinical history and physical examination, as well as a test called a filipin staining test, which can detect cholesterol in the skin cells. A genetic test can identify defects in the NPC1 and NPC2 genes. 
  • Treatment: There is no cure for Niemann-Pick type C. Treatment is directed towards relieving the symptoms, providing pain control, and maximizing comfort.
  • Cause: Neimann-Pick type C is a bit different from types A and B. There is a shortage of proteins that are associated with the transfer and processing of sphingomeylin. This protein shortage results in an accumulation of sphingomyelin, which then builds up in many organs of the body, causing the symptoms.
  • Genetics: A defect of either the NPC1 or NPC2 gene results in the protein shortage characteristic of Niemann-Pick type C. As with the other types of Niemann-Pick disease, this is an autosomal recessive disorder which means that a child or adult with the disease must inherit the genes from both parents (who typically do not have the disease themselves).

Niemann-Pick Type D

This variant is sometimes considered to be the same disease as type C. It was initially recognized in a small population in Nova Scotia, and thought to be a different variant of Niemann-Pick disease, but since then, this group has been found to have the same disease characteristics and genetics of Niemann-Pick type C. 

Research

There is ongoing research into treatment options for Niemann-Pick disease. Replacement of the deficient enzyme has been studied. At the current time, this type of therapy is only available by enrollment in a clinical trial. You can find information about how to participate in clinical trials by asking your doctor or by contacting Niemann-Pick advocacy and support organizations.

A Word From Verywell

Niemann-Pick disease causes a number of symptoms that interfere with having a normal life, and cause a great deal of discomfort, pain and disability. It is very stressful for the whole family when such a serious illness becomes a part of your life.

If you or your child has been diagnosed with Niemann-Pick disease, the lifelong affliction means that your family must find a strong support network, and a wide variety of professionals to provide multidisciplinary care. Because it is a rare disease, you may need to search to locate professionals who are experienced in providing the services that you need.

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