Niemannpick disease merck manuals consumer version. The gene responsible for this disorder is recessive, which means that children with niemannpick disease have inherited an. Andrew lieberman, md phd abrams collegiate professor of pathology director of neuropathology university of michigan medical school 3510 msrb 1, 1150 w. Diagnostic workup and management of patients with suspected. Niemannpick np disease is caused by an abnormality in lysosomes, which are unable to degrade macromolecules. Deficiencies of asm lead to destruction of nerve cells. Niemannpick disease type b is an allelic disorder characterized by visceral involvement only and survival into adulthood. It has a wide range of symptoms that vary in severity. Niemannpick disease is a medical hereditary disorder, where a specific enzyme deficiency causes a product of fat sphingomyelin metabolism accumulation.
A biochemical disorder affecting a lipid fat called sphingomyelin, resulting usually in progressive enlargement of the liver and spleen hepatosplenomegaly, swollen glands lymphadenopathy, anemia and mental and physical deterioration. Now that siamese cats are available as genetic models for niemannpick disease, indepth studies on the biochemical properties of the disease are being performed. In niemannpick disease, harmful quantities of lipids accumulate in. Niemannpick disease type b genetic and rare diseases. Niemannpick type c npc disease is a neurovisceral disorder caused by mutations in the npc1 and npc2 genes. Mayo clinic doctors are wellacquainted with this complicated disease and are experienced at distinguishing niemannpick from other diseases with similar symptoms. Niemannpick disease forum questions about niemannpick disease ask a question and get answers from other users.
Ppt niemannpick disease powerpoint presentation free. Mutations that produce defective npc1 protein, a cholesterol trafficking protein, lead to accumulation of unesterified. Niemann pick disease type c npc is a progressive lysosomal storage disorder caused by mutations in the npc1 in 95% of cases or npc2 in 5% of cases genes, inherited in an autosomal. The purpose of this study is to assess the efficacy and safety of arimoclomol compared to placebo when it is administered as an addon therapy to the patients current prescribed best standard. Lipids fatty materials such as waxes, fatty acids, oils, and cholesterol and proteins are usually broken down into smaller components to provide energy for the body. It can result from a deficiency of the acid sphingomyelinase enzyme, leading to type a or b disease, or the npc1 or npc2 also called he1 proteins involved. Niemannpick disease is type of lysosomal storage disorder. Niemann pick disease npd is an inherited disorder that is due to defects in an enzyme called acid sphingomyelinase. Niemannpick disease types a and b are now considered a distinct disorder called acid. Npd type a is known as the neurological type, which appears during infancy, with intellectual disability and death in early.
Autosomal recessive lysosomal storage disease caused by deficient activity of the enzyme acid sphingomyelnase asm, leading to accumulation of sphingomyelin, cholesterol, and several other lipids within lysosomes and in cell membranes. The biochemical nature of type e still awaits clarification. People with niemannpick disease have an abnormal lipid fat metabolism which causes lipids to buildup in the spleen, lung, liver, bone marrow, and brain. Approximately 1 in 90 persons of ashkenazi jewish descent are carriers for niemannpick disease. Dna of niemannpick disease victims might offer clues in. The three most commonly recognized forms are niemann pick types a and b asmd or acid sphingomyelinase deficiency and niemannpick disease type c npc the national niemannpick disease foundation nnpdf supports and promotes research to find treatments and. Niemann pick disease type c nord national organization for. Drugsendocrinologicandmetabolicdrugsadvisorycommitteeucm248677. Type a presents in early childhood and follows a severe, neurodegenerative course leading to death before age 5. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adultonset chronic neurodegenerative disease. The socalled lactosylceramidosis is a rare variant pertinent to this group. These types are classified on the basis of genetic cause and the signs and symptoms of the condition. A free powerpoint ppt presentation displayed as a flash slide show on id. Niemannpick type c disease npc is an autosomal recessive, inherited lysosomal storage disorder that leads to abnormal accumulation of cholesterol and other lipids in late endosomes and lysosomes lely.
A prospective, randomised, doubleblind, placebo controlled therapeutic study in patients with confirmed diagnosis of niemannpick disease type c npc. Cyclodextrin for niemannpick type c1 disease national. It may or may not involve the nervous system and breathing. Niemannpick disease type c orphanet journal of rare. Consensus clinical management guidelines for niemannpick.
Niemannpick type c npc is a progressive and life limiting autosomal recessive disorder caused by mutations in either the npc1 or npc2 gene. Niemannpick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. People with this condition experience a build up of lipids in the spleen, liver, lungs, bone marrow, and brain. Niemannpick disease alex gavlin and brad kligman niemannpick is an autosomal recessive genetic disorder resulting in abnormal lipid metabolism. Picks disease is a condition closely related to frontotemporal lobar degeneration ftld and is one of the rarer types of dementia. Ucsf niemannpick disease trial arimoclomol prospective. Treatment of niemannpick type c disease by histone. Acid sphingomyelinase deficiency niemannpick disease market focus 2015 this report provides comprehensive information on the therapeutic development for acid sphingomyelinase deficiency niemannpick disease, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action moa, route of administration roa and molecule type, along with. Signs and symptoms may include enlarged liver and spleen hepatosplenomegaly, reduced growth, frequent lung infections, and reduced numbers of blood cells involved in clotting platelets.
Each one can cause different symptoms and may occur at different. Niemannpick disease information page national institute. Npd type a, neurodegenerative form, occurs in infants. Niemannpick disease results from a deficiency of sphingomyelinase that causes accumulation of sphingomyelin in the cells of the reticuloendothelial and central nervous systems. Niemannpick disease npd refers to a group of inherited metabolic disorders known as the leukodystrophies or lipid storage diseases in which harmful quantities of a fatty substance lipids accumulate in the spleen, liver, lungs, bone marrow, and the brain.
George december 5, 2005 the disease condition involving the breakdown and use of fats and cholesterol in the body harmful amounts of. Niemannpick disease type c1, a lipid storage disorder, as seen in a mouse cerebellum nichd an experimental drug appears to slow the progression of niemannpick disease type c1 npc1, a fatal neurological disease, according to results of a clinical study led by researchers at the national institutes of health. Isabel and toni now lead the niemannpick support groups in spain fundacion niemannpick and the uk niemannpick disease group respectively. Pdf the following is a case of niemannpick disease npd type b associated with a psychiatric disorder. Niemann pick is a rare, inherited disease that affects the bodys ability to metabolize fat cholesterol and lipids within cells. Pdf niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage.
Niemannpick disease, a lysosomal storage disease, is more common among some ethnic groups, including ashkenazi jews, north africans, arabs, and turks niemannpick disease type a, the most common form, is caused by mutations in the acid sphingomyelinase asm gene smpd1. Niemann pick disease type a and b occur due to the deficiency of an enzyme called acid sphingomyelinase. Diagnosis of niemannpick diseasenational niemannpick. The adult form type b disease, which appears during the second. Niemannpick disease type c also known as npc is a fatal, neurodegenerative disease that affects 1 in 120,000 however these numbers are growing. This blood test identifies four mutations associated with niemannpick diseases, type a and b. Type c is a lipidosis that is caused by a build up of cholesterol and other fats lipids in the cells. Np disease encompasses a set of autosomal recessive hereditary abnormalities characterized by the accumulation of lipids, mostly sphingomyelin and cholesterol, in different. Type a npd patients exhibit hepatosplenomegaly in infancy and profound central nervous system. To reduce the time needed for niemannpick type c npc diagnosis. Signs and symptoms typically develop in the preteen years and may include enlarged liver and spleen hepatosplenomegaly, short stature, problems with lung function including frequent lung infections. The mutations for types a and b have been extensively studied, particularly among the ashkenazi jewish population, and dna tests for these forms of niemannpick disease are available help by tradece potter. Two distinct metabolic derangements are encompassed under the eponym niemannpick disease npd. Antenatal diagnosis diagnosis in the fetus of niemannpick.
View reference source for the article along with the name of the writer and the editor for the article on niemannpick disease. It is considered a lysosomal storage disorder because people with npd have lysosomes the cells recycling center that cannot break down certain types of fats. This condition leads to abnormal accumulation of lipids in spleen, liver, lungs, bone marrow, and brain. Mayo clinic doctors with expertise in niemannpick work together to provide exactly the care you need. Experimental treatment for niemannpick disease type c1. Niemannpick disease an overview sciencedirect topics.
Niemannpick disease type c npc is a hugely lifelimiting neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen. Niemannpick disease is a group of severe inherited metabolic disorders, in which sphingomyelin accumulates in lysosomes in cells the lysosomes normally transport material through and out of cells these disorders involve the dysfunctional metabolism of sphingolipids, which are fats found in cell membranes so it is a kind of sphingolipidosis, which is included in the larger family of. Carriers have one normal and one defective npc gene and are symptomfree. With this type of inherited disease, there is a 25% chance that each child of. At least some types are characterized by foamy reticular cells containing phospholipids. Niemannpick disease type c npc is a rare progressive genetic disorder. The three most commonly recognized forms are niemannpick types a and b asmd or acid sphingomyelinase deficiency and niemannpick disease type c npc. Approximately 95 percent of cases are caused by mutations of the npc1 gene, and the remaining 5 percent are caused by mutations in the npc2 gene.
The lipid accumulation can be seen in tissues throughout the body, but the major diseaseassociated pathologies are due to progressive neurological. Niemannpick is a debilitating disease that retards movement and development of an infants ability to think and reason, as if they had a kind of pediatric alzheimer disease. This presentation is brought to you for free and open access by lvhn scholarly works. Niemannpick disease is a condition that affects many body systems. Niemannpick c disease npc is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1120 000 live births. At npuk we are dedicated to supporting the individuals and families affected by these conditions.
One type of niemannpick histiocyte with large grayblue granules. People with this condition experience symptoms related to. It affects people of all ages from newborns to adults. 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. Niemannpick disease type b is an inherited condition involving lipid metabolism. Niemannpick disease is an inherited disease that affects lipid metabolism, or the way fats, lipids, and cholesterol are stored in or removed from your body. Unlike alzheimers disease and some other forms of dementia, it usually affects people between 40 and 60. Splenomegaly was the most common presenting feature 78%. Niemannpick diseases are a subgroup of lipid storage disorders called sphingolipidoses in. Niemannpick disease is a lysosomal storage disorder that is characterized by failure to thrive and enlargement of the liver and spleen hepatosplenomegaly. The neurological involvement defines the disease severity in most patients but is typically preceded by. Niemannpick type c disease lvhn scholarly works lehigh. Pdf niemann pick disease a case report researchgate.
Travis stork explains how niemannpick disease affects the body. The diseas e is caused by deficiency of enzyme, acid sphingomyelinase asm. A prospective, longitudinal study of the natural history. Niemannpick disease is hereditary and follows an autosomal recessive pattern the classical form of the disease is niemann. Niemannpick disease np refers to a group of inherited metabolic disorders known as lipid storage diseases. One of these groups aims is to raise awareness among doctors of a disorder most have never heard of 1, so they can diagnose it sooner and put families in touch with support groups for help. Niemannpick disease npd niemannpick disease is an inherited condition that affects many different parts of the body. A clinical trial to evaluate a drug candidate called cyclodextrin as a possible treatment for niemannpick disease type c1 npc, a rare and fatal genetic disease, will start today, researchers. The niemann pick type c1 npc1 gene is responsible for most 95% cases of npc disease1 npc1 is located on chromosome 18 at cytogenetic band 18q11122,3 npc2 is mapped at chromosome 14q24. Niemann pick disease can affect the brain, nerves, liver, spleen, bone marrow and, in severe cases, lungs. Types a and b are sphingolipidoses and are caused by a buildup of sphingomyelin in the tissues. Niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage.
Niemannpick disease, type c definition of niemannpick. Niemannpick disease is divided into four main types. Niemannpick disease npd is a group of inherited metabolic disorders in which harmful quantities of a fatty substance lipids accumulate in the spleen, liver, lungs, bone marrow, and brain. Niemannpick disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. Niemannpick disease type a genetic and rare diseases nih. Previously, studies on niemannpick disease were performed on rodents with druginduced enzyme deficiencies, which was less than ideal.
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