Niemann-Pick Disease Overview
Niemann-Pick disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. The most commonly recognized forms are Niemann-Pick ASMD (types A and B or Acid Sphingomyelinase Deficiency) and NPC (type C). The National Niemann-Pick disease Foundation (NNPDF) supports and promotes research to find treatments and a cure for all types of Niemann-Pick disease, and provides support services for individuals and families affected by NPD. Our Vision is a world where Niemann-Pick disease is no longer a threat to a full and productive life for patients and their families. Membership in the NNPDF is free and helps ensure we can keep families affected by Niemann-Pick disease up to date with all the latest news and research information – please complete our NNPDF Membership Form. Membership is open to families affected by Niemann-Pick disease, extended family, friends, and community supporters.
Niemann-Pick Disease Types
Niemann-Pick disease affects all segments of the population with cases reported in North America, South America, Europe, Africa, Asia, and Australia. However, a higher incidence of NPD has been found in certain populations:
- Ashkenazi Jewish population (NPA and NPB)
- French Canadian population of Nova Scotia (Type D, now considered a variant of Type C or NPC)
- Maghreb region (Tunisia, Morocco, and Algeria) of North Africa (NPB)
- Spanish-American population of southern New Mexico and Colorado (NPC)
Please continue reading below for more information about each type of Niemann-Pick disease (NPD). We invite you to contact the NNPDF if you would like further information or if you have any questions about NPD. We are here to provide information, support and referrals and to advance essential research into effective treatments and a cure.
ASMD Types A (NPA) and B (NPB)
Niemann-Pick ASMD Types A and B (NPA and NPB) are caused by the deficiency of a specific enzyme, acid sphingomyelinase (ASM). This enzyme is found in special compartments within cells called lysosomes and is required to metabolize a lipid called 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.
NPA and NPB are both caused by the same enzymatic deficiency and there is growing evidence that the two forms represent opposite ends of a continuum. People with NPA generally have little or no ASM production (less than 1% of normal) while those with NPB have approximately 10% of the normal level of ASM.
Forms of ASMD between these two extremes do occur, and the diagnosis is sometimes called intermediate NPD or Type A/B. There can be considerable overlap along the entire ASMD disease spectrum with symptoms ranging in onset, complexity and severity, and every patient’s case is unique.
The clinical prognosis for NPA and NPB patients is very different. NPA is a severe neurologic disease that leads to an early death, usually by 2 to 4 years of age. In contrast, patients with NPB generally have little or no neurologic involvement and may survive into adulthood, though there may be health complications. Type B individuals usually have enlarged livers and spleens, and respiratory problems are common. The enlargement of organs and the respiratory problems can cause cardiovascular stress and can lead to heart disease.
There are approximately 1,200 cases of NPA and NPB worldwide with the majority being Type B or an intermediate form.
Type C (NPC)
Niemann-Pick Type C (NPC) is very different than Type A or B (ASMD). NPC Patients are not able to metabolize cholesterol and other lipids properly within the cell. Consequently, excessive amounts of cholesterol accumulate within the liver and spleen and excessive amounts of other lipids accumulate in the brain. NPC causes a secondary reduction of ASM activity, which led all three types to be considered forms of the same disease.
There is considerable variation in when Type C symptoms first appear and in the progression of the disease. Symptoms may appear as early as a few months of age or as late as adulthood.
Vertical gaze palsy (the inability to move the eyes up and down), enlarged liver, enlarged spleen, or jaundice in young children are strong indications that NPC should be considered. It is common for only one or two symptoms to appear in the early stages of the disease.
In most cases, neurological symptoms begin appearing between the ages of 4 and 10. Generally, the later neurological symptoms begin, the slower the progression of the disease.
Type C Niemann-Pick Disease has an estimated 500 cases diagnosed worldwide. It is believed, however, that the number of people affected by NPC is higher, but diagnostic difficulties do not allow an accurate assessment of the occurrence rate. NPC has been initially diagnosed as a learning disability, mild retardation, “clumsiness,” and delayed development of fine motor skills. It is not uncommon for a family to spend several years seeking a diagnosis before NPC is identified.
NPC is always fatal. The majority of children with NPC die before age 20 (many die before the age of 10). Late onset of symptoms can lead to longer life spans but it is extremely rare for any person with NPC to reach age 40.
Diagnosis of Niemann-Pick Disease
Is someone you know experiencing some of these symptoms?
Abdominal enlargement; Enlarged spleen or liver; Jaundice following birth; Unusual shortness of breath; Repeated lung infections; Cherry red spot inside the eye; Vertical eye movement difficulties; Progressive loss of early motor skills; Feeding and swallowing difficulties; Learning problems; Sudden loss of muscle tone; Slurred speech; Seizures; Hypersensitivity to touch.
These symptoms may be an indication of Niemann-Pick disease. Chances are you haven’t heard much about Niemann-Pick Disease. It’s a rare disease, but maybe not as rare as we think as it is difficult to diagnose.
All types of Niemann-Pick Disease are autosomal recessive, which means that children with the disease have two copies of the abnormal gene. Each parent carries one copy of the abnormal gene without having any signs of the disease themselves. Siblings of the parents may also be carriers of the abnormal gene.
When both parents are carriers of the abnormal gene, there is:
- a 1 in 4 chance that a child will have the disease
- a 1 in 2 chance that a child will be a carrier
- a 1 in 4 chance that a child will not have the disease and will not be a carrier
Carrier detection testing for all families is not yet reliable.
The mutations for Types A and B have been extensively studied, particularly among the Ashkenazi Jewish population, and DNA tests for these forms of Niemann-Pick Disease are available (help by tradece potter). Antenatal diagnosis (diagnosis in the fetus) of Niemann-Pick Disease is available in a limited number of centers.
Dr. Wenda Greer of Dalhousie University has identified the genetic mutation related to Type D (now called the Nova Scotia variant of NPC). Carrier detection tests can be conducted for this mutation and is possible for other families only after their specific mutation is identified.
Pick’s Disease or Frontotemporal Dementia, unrelated to Niemann-Pick disease, is sometimes confused with Niemann-Pick disease. Because the NNPDF occasionally receives inquiries about Pick’s Disease, as a courtesy, a few resource for Pick’s Disease have been provided.