What is Niemann-Pick?
Although not widely known by the public and classified as rare by medical science, Niemann-Pick Disease (NPD) Type C has been the subject of worldwide medical research for many years because it is considered an important link in the battles against heart disease, Alzheimer’s, stroke & seizure disorders. Basically, an inherited biochemical deficiency results in the body’s inability to metabolize cholesterol properly. Consequently, cholesterol begins to accumulate in the liver, the spleen and the brain - a process which eventually results in serious neurological damage. The pathological effects of this disease were first noted around the turn of the century but, of course, its origins go back much further in time. In fact, a closely related variant of NPD-C (known as Type D) has been traced back to its originators in Nova Scotia in the mid- 1700’s. With the discovery last summer of the primary gene associated with NPD-C medical research has intensified worldwide, and at least one drug has been found which delays the onset of serious effects but it is not yet ready for clinical trials. (Apparently, life as a little mouse does have its advantages). Usually, the effects of Niemann-Pick Disease Type C (deterioration of motor skills, slurred speech, etc.) don’t appear until the early school years (although there is also a young adulthood onset type). Children seldom survive beyond their 15th birthday. In some cases, the prognosis is more difficult because of his early age, but serious effects could begin in as few as two years. |
Gabrielle LaVerde |
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What is Niemann-Pick? Why is it a Child Killer? |
What is Niemann-Pick disease?Niemann-Pick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. In people with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain.
This disorder is divided into four main types based on the genetic cause and the signs and symptoms. Niemann-Pick disease type A appears during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to gain weight and grow at the expected rate (failure to thrive), and progressive deterioration of the nervous system. Due to the involvement of the nervous system, Niemann-Pick disease type A is also known as the neurological type. Children affected by this condition generally do not survive past early childhood.
Niemann-Pick disease type B has a range of features that may include:
hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as elevated levels of cholesterol and other lipids (fats), and decreased numbers of blood cells involved in clotting (platelets). Niemann-Pick disease type B is also known as the non-neurological type because the nervous system is not usually affected. People with Niemann-Pick disease type B usually survive into adulthood. Niemann-Pick disease type C usually appears in childhood, although infant and adult onsets are possible. Signs of Niemann-Pick disease type C include severe liver disease, breathing difficulties, developmental delay, seizures, poor muscle tone (dystonia), lack of coordination, problems with feeding, and an inability to move the eyes vertically. People with this disorder can survive into adulthood. Niemann-Pick disease type C is further subdivided into types C1 and C2, each caused by a different gene mutation. (more) |
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What is Niemann-Pick Disease?Niemann-Pick disease is an autosomal recessive disorder affecting lipid metabolism (the breakdown and use of fats and cholesterol in the body), in a way which causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain.
There are three variants of Niemann-Pick disease based on the genetic cause and the symptoms exhibited by the patient.
GeneticsMutations in the NPC1, NPC2, and SMPD1 genes cause Niemann-Pick disease. This condition is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. If both parents are carriers, there is a 25% chance with each pregnancy for an affected child. Genetic counseling and genetic testing is recommended for families who may be carriers of Niemann-Pick.
Type CType C is characterized by onset in childhood, although infant and adult onsets are possible. Other signs include severe liver disease, breathing difficulties, developmental delay, seizures, increased muscle tone (dystonia), lack of coordination, problems with feeding, and an inability to move the eyes vertically. People with this disorder can survive into adulthood. The incidence of Niemann-Pick disease, type C is estimated to be 1 in 150,000 people. The disease occurs more frequently in people of French-Acadian descent in Nova Scotia. Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease, type C. The NPC1 gene produces a protein that is located in membranes inside the cell and is involved in the movement of cholesterol and lipids within cells. A deficiency of this protein leads to the abnormal build up of lipids and cholesterol within cell membranes. The NPC2 gene produces a protein that binds and transports cholesterol, although its exact function is not fully understood.
Biochemical TransportThe molecular basis for this disease is extremely complex due to the role that endosome formation has on affected patients. Recently, three theories have attempted to explain the buildup of cholesterol in the lysosomes of affected patients of Niemann-Pick Disease Type C due to the malfunction of the protein NPC-1.
The contention by Neufel et al is that the buildup of mannose 6-phosphate receptors (MPRs) in the late endosome suggests that the retrograde breakdown of cholesterol via the Trans Golgi Network cannot occur.[1]
Another theory suggests that the blockage of retrograde cholesterol breakdown in the late endosome is due to decreased membrane elasticity and thus the return vesicles of cholesterol to the Trans Golgi Network cannot bud and form.
The support of these theories has considerable evidence using mutant proteins in vitro to determine the buildup of cholesterol in the lysosomes. Researchers have also discovered that the NPC-1 protein may function as a pump of cholesterol.[2]
The overall effect of a malfunction in NPC-1 is that low levels or an absence of the protein lead to the abnormal accumulation of lipids and cholesterol in the cells of people with this condition.
External linksNational Niemann-Pick Disease Foundation Ara Parseghian Medical Research Foundation Niemann-Pick Disease Group (UK) This article incorporates public domain text from The U.S. National Library of Medicine
References^ Neufeld EB, Wastney M, Patel S, et al (1999). "The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo". J. Biol. Chem. 274 (14): 9627-9635. PMID 10092649. ^ Davies JP, Chen FW, Ioannou YA (2000). "Transmembrane molecular pump activity of Niemann-Pick C1 protein". Science 290 (5500): 2295-2298. doi:10.1126/science.290.5500.2295. PMID 11125140. |
Types A and BType A Niemann-Pick disease begins during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to thrive, and progressive deterioration of the nervous system. Children affected by this condition generally do not survive past early childhood. 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 people. The incidence for other populations is unknown. Type B disease may include signs of hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cells involved in clotting (platelets). People affected by this type of Neimann Pick disease usually survive into adulthood. Niemann-Pick disease, type B occurs in all populations. Mutations in the SMPD1 gene cause Niemann-Pick disease, types A and B. This gene carries instructions for cells to produce an enzyme called acid sphingomyelinase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it processes lipids such as sphingomyelin. Mutations in this gene lead to a deficiency of acid sphingomyelinase and the accumulation of sphingomyelin, cholesterol, and other kinds of lipids within the cells and tissues of affected individuals. |
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Important News and Links for Parents:
http://blog.mlive.com/citpat/2008/04/girls_family_hoping_for_a_cure.html
ABC News, Controversial Stem Cell Treatment Attracts Thousands, 02/20/2008 http://abcnews.go.com/Health/story?id=3931445&page=1
Chemical Chaperone Could Open Door to Treatment of Neurological Disorder, 02/05/2008 http://www.medicalnewstoday.com/articles/96165.php
BioCell™ http://www.biocellcorp.com/products_bluei.htm
Mirror.co.uk “Tragic six-year-old is struck down Alzheimer’s Disease, 01/31/2008 http://www.mirror.co.uk/news/topstories/2008/01/31/only-6-and-leah-s-got-alzheimer-s-89520-20303924/
Guardian.co.uk, Surgeons Attempt to Repair Hearts with Stem Cell Injections, 01/23/2008 http://www.guardian.co.uk/science/2008/jan/23/stemcells.genetics1?gusrc=rss&feed=networkfront
The Capital Times, Thomason: Massive Stem Cell Investment Needed to Catch California, 01/22/2008 http://www.madison.com/tct/news//index.php?ntid=268672
News-Medical.Net, Stem Cell Therapy Restores Muscle Function in Mice with Muscular Dystrophy, 01/21/2008 http://www.news-medical.net/?id=34569
MedicineNet.com, Cholesterol Durg Zetia Doesn’t Cut Heart Attack Risk: Study, January 14, 2008 http://www.medicinenet.com/script/main/art.asp?articlekey=86417
Medical News Today, Potential Stem Cell Treatments Following Discovery of “Creator” Gene For Cerebral Cortex, 01/18/2008 http://www.medicalnewstoday.com/articles/94435.php
Oregon Health & Science University, Doernbecher Children’s Hospital Team Completes First-Ever Stem Cell Transplant in Human Brain, first stem cells recipient goes home, 12/12/2006 |
Who is Gabrielle LaVerde?
Gabrielle LaVerde is a delightful and adored 7 year old little girl who has been diagnosed with a fatal and rare disease, called Niemann-Pick Type C. The disease is considered an orphan disease since there have only been 500 known cases worldwide. The disease itself renders its victims with Alzheimer’s-like symptoms—victims move backward in time and forget how to perform basic functions, such as talking, walking, eating, chewing, swallowing, and breathing.
We first learned of Gabrielle’s diagnosis in October, 2007. Gabrielle’s elementary school classmates were horrified to learn that her disease was fatal, and that there was no cure, no miracle drug, or no surgery that could save her. Her classmates quickly rallied support, not only from their parents, but from the entire Deltona community to help pay for experimental treatments. The outpouring amount of encouragement, support, and prayers that the LaVerde family has received has been phenomenal. The elementary school students raised over $10,800 in less than 3 months.
The purpose of this website is to:
· Increase awareness of the disease known as Niemann-Pick Type C · Create awareness about Gabrielle LaVerde’s condition · Share with supporters recent and upcoming events to help Gabrielle. · Special Thanks to Lloyd Marcus, Deltona Lakes Elementary School, the City of Deltona, and the citizens of Deltona, for your ongoing support.
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More Informative Links:
http://abcnews.go.com/Health/story?id=3931445&page=1 http://www.medicalnewstoday.com/articles/96165.php http://www.biocellcorp.com/products_bluei.htm http://www.mirror.co.uk/news/topstories/2008/01/31/only-6-and-leah-s-got-alzheimer-s-89520-20303924/) http://www.guardian.co.uk/science/2008/jan/23/stemcells.genetics1?gusrc=rss&feed=networkfront http://www.madison.com/tct/news//index.php?ntid=268672 http://www.news-medical.net/?id=34569 http://www.medicinenet.com/script/main/art.asp?articlekey=86417 http://www.centredaily.com/business/story/330246.html http://www.medicalnewstoday.com/articles/94435.php http://www.ohsu.edu/stemcellstrial/ |
Gabrielle is moving backward in time |
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