Niemann pick disease can affect the brain, nerves, liver, spleen, bone marrow and, in severe cases, lungs. Niemann pick disease type a and b occur due to the deficiency of an enzyme called acid sphingomyelinase. Niemannpick disease type c npc is a hugely lifelimiting neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen. The three most commonly recognized forms are niemannpick types a and b asmd or acid sphingomyelinase deficiency and niemannpick disease type c npc. Npd type a is known as the neurological type, which appears during infancy, with intellectual disability and death in early. Niemannpick type c disease lvhn scholarly works lehigh. Type a presents in early childhood and follows a severe, neurodegenerative course leading to death before age 5. Mayo clinic doctors are wellacquainted with this complicated disease and are experienced at distinguishing niemannpick from other diseases with similar symptoms. 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 a genetic and rare diseases nih. Type a npd patients exhibit hepatosplenomegaly in infancy and profound central nervous system. Niemann pick disease type c nord national organization for. Niemannpick disease is hereditary and follows an autosomal recessive pattern the classical form of the disease is niemann.
One type of niemannpick histiocyte with large grayblue granules. 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. 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. People with this condition experience symptoms related to. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adultonset chronic neurodegenerative disease. The first is due to the deficient activity of the lysosomal enzyme acid sphingomyelinase asm. 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. 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. Previously, studies on niemannpick disease were performed on rodents with druginduced enzyme deficiencies, which was less than ideal. We offer practical and emotional support, provide information and strive to raise. Npd type a, neurodegenerative form, occurs in infants.
Niemannpick disease is a lysosomal storage disorder that is characterized by failure to thrive and enlargement of the liver and spleen hepatosplenomegaly. Picks disease is a condition closely related to frontotemporal lobar degeneration ftld and is one of the rarer types of dementia. George december 5, 2005 the disease condition involving the breakdown and use of fats and cholesterol in the body harmful amounts of. Pdf niemann pick disease a case report researchgate. Niemannpick disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. Niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage. 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. Treatment of niemannpick type c disease by histone. The biochemical nature of type e still awaits clarification.
View reference source for the article along with the name of the writer and the editor for the article on niemannpick disease. Consensus clinical management guidelines for niemannpick. 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. Unlike alzheimers disease and some other forms of dementia, it usually affects people between 40 and 60. Niemannpick disease npd is a group of diseases passed down through families inherited in which fatty substances called lipids collect in the cells of the spleen, liver, and brain.
Ucsf niemannpick disease trial arimoclomol prospective. 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. To reduce the time needed for niemannpick type c npc diagnosis. Drugsendocrinologicandmetabolicdrugsadvisorycommitteeucm248677. Pronunciation of niemannpick disease with 1 audio pronunciation, 4 synonyms, 1 meaning, 11 translations and more for niemannpick disease. 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. 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. Niemannpick disease type b is an allelic disorder characterized by visceral involvement only and survival into adulthood. Niemannpick disease is a condition that affects many body systems. It may or may not involve the nervous system and breathing. Niemannpick type c npc is a progressive and life limiting autosomal recessive disorder caused by mutations in either the npc1 or npc2 gene.
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. Niemannpick disease information page national institute. Niemannpick disease type c orphanet journal of rare. 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.
Deficiencies of asm lead to destruction of nerve cells. Niemannpick np disease is caused by an abnormality in lysosomes, which are unable to degrade macromolecules. Approximately 1 in 90 persons of ashkenazi jewish descent are carriers for niemannpick disease. It has a wide range of symptoms that vary in severity. A free powerpoint ppt presentation displayed as a flash slide show on id. Travis stork explains how niemannpick disease affects the body. Pdf the following is a case of niemannpick disease npd type b associated with a psychiatric disorder. Niemannpick diseases are a subgroup of lipid storage disorders called sphingolipidoses in. 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.
Niemannpick disease types a and b are now considered a distinct disorder called acid. Niemannpick disease type c1 is an autosomal recessive, neurodegenerative disease with a frequency of one in 120,000 live births. 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. Niemannpick disease an overview sciencedirect topics.
Niemannpick disease results from a deficiency of sphingomyelinase that causes accumulation of sphingomyelin in the cells of the reticuloendothelial and central nervous systems. Niemann pick is a rare, inherited disease that affects the bodys ability to metabolize fat cholesterol and lipids within cells. Niemannpick disease merck manuals consumer version. Carriers have one normal and one defective npc gene and are symptomfree. Type c is a lipidosis that is caused by a build up of cholesterol and other fats lipids in the cells. The diseas e is caused by deficiency of enzyme, acid sphingomyelinase asm.
Np disease encompasses a set of autosomal recessive hereditary abnormalities characterized by the accumulation of lipids, mostly sphingomyelin and cholesterol, in different. Niemannpick c disease npc is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1120 000 live births. Niemannpick disease type c npc is a rare progressive genetic disorder. This condition leads to abnormal accumulation of lipids in spleen, liver, lungs, bone marrow, and brain. Niemann pick disease npd is an inherited disorder that is due to defects in an enzyme called acid sphingomyelinase.
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. Types a and b are sphingolipidoses and are caused by a buildup of sphingomyelin in the tissues. At npuk we are dedicated to supporting the individuals and families affected by these conditions. These types are classified on the basis of genetic cause and the signs and symptoms of the condition. Niemannpick disease is divided into four main types.
The adult form type b disease, which appears during the second. 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. Diagnosis of niemannpick diseasenational niemannpick. 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. 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. 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. Cyclodextrin for niemannpick type c1 disease national. 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. Niemannpick disease, type c definition of niemannpick. Experimental treatment for niemannpick disease type c1.
It affects people of all ages from newborns to adults. 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. Pdf niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage. Ppt niemannpick disease powerpoint presentation free. Niemannpick disease npd niemannpick disease is an inherited condition that affects many different parts of the body. Niemannpick type c npc disease is a neurovisceral disorder caused by mutations in the npc1 and npc2 genes. Mutations that produce defective npc1 protein, a cholesterol trafficking protein, lead to accumulation of unesterified.
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. 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. A prospective, randomised, doubleblind, placebo controlled therapeutic study in patients with confirmed diagnosis of niemannpick disease type c npc. Npc is a rare genetic disease where lipids fats build up in the liver, spleen and brain impeding. Dna of niemannpick disease victims might offer clues in. Now that siamese cats are available as genetic models for niemannpick disease, indepth studies on the biochemical properties of the disease are being performed. Diagnostic workup and management of patients with suspected. Splenomegaly was the most common presenting feature 78%. At least some types are characterized by foamy reticular cells containing phospholipids. The lipid accumulation can be seen in tissues throughout the body, but the major diseaseassociated pathologies are due to progressive neurological.
This presentation is brought to you for free and open access by lvhn scholarly works. The neurological involvement defines the disease severity in most patients but is typically preceded by. Antenatal diagnosis diagnosis in the fetus of niemannpick. The socalled lactosylceramidosis is a rare variant pertinent to this group.
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. Niemannpick disease np refers to a group of inherited metabolic disorders known as lipid storage diseases. Niemannpick disease is type of lysosomal storage disorder. Niemannpick disease is a medical hereditary disorder, where a specific enzyme deficiency causes a product of fat sphingomyelin metabolism accumulation.
Mayo clinic doctors with expertise in niemannpick work together to provide exactly the care you need. People with niemannpick disease have an abnormal lipid fat metabolism which causes lipids to buildup in the spleen, lung, liver, bone marrow, and brain. Niemannpick disease type b genetic and rare diseases. A prospective, longitudinal study of the natural history. Two distinct metabolic derangements are encompassed under the eponym niemannpick disease npd. 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. 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. Niemannpick disease alex gavlin and brad kligman niemannpick is an autosomal recessive genetic disorder resulting in abnormal lipid metabolism. Niemannpick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. In niemannpick disease, harmful quantities of lipids accumulate in. Each one can cause different symptoms and may occur at different. 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. Niemannpick disease type b is an inherited condition involving lipid metabolism.
524 677 882 1363 231 293 1497 1372 1163 765 993 20 254 1520 866 1097 277 843 748 1400 132 436 507 293 1396 1006 1184 420 240 199 1367 134 428 882 431 161 96 129 872 658 990 999