The disorders are inherited in an autosomal recessive pattern and result in the accumulation of sphingomyelin in various organs including the spleen, liver, lungs, bone marrow and brain. The recently incorporated, vtesse, a rare disease company spunoff from cydan development, inc. Magnetic resonance imaging revealed splenomegaly of 23. A 54yearold man with niemannpick disease type b with chronic transaminitis, thrombocytopenia, and splenomegaly for 21 years presented with abdominal discomfort. Mayo clinic doctors are wellacquainted with this complicated disease and are experienced at distinguishing niemann pick from other diseases with similar symptoms. Niemannpick disease overview national niemannpick disease. Apr 07, 2016 niemann pick disease type c2 is a rare metabolic condition that affects many different parts of the body. A recent case report demonstrated a delay in diagnosis of eight years when a patient with npc presented with. An inherited disorder of lipid metabolism characterized by the accumulation of lipids in the spleen and liver and sometimes in the lungs, bone marrow.
The authors show that npc1 regulates calcium levels in the lysosome, and calcium dysregulation could be. Mayo clinic doctors with expertise in niemannpick work together to provide exactly the care you need. This means that both the mother and the father must pass on the defective form of the gene for the child to be affected. It has a wide range of symptoms that vary in severity. Niemannpick disease leads to the irregular and harmful accumulation of fatty substances within various tissues of the body, including liver, spleen, and brain tissue. Niemannpick disease overviewnational niemannpick disease. Niemann pick disease type c npc is a rare progressive genetic disorder characterized by an inability of the body to transport cholesterol and other fatty substances lipids inside of cells.
Niemannpick disease np refers to a group of inherited metabolic disorders known as lipid storage diseases. Mayo clinic doctors with expertise in niemann pick work together to provide exactly the care you need. The incidence of niemannpick disease type c is estimated to be one in 150,000. The original description of npd referred to what is currently termed npd type a, which is a fatal disorder of early childhood characterized by failure to thrive, hepatosplenomegaly, and a rapidly progressive ne. Niemannpick disease type c npc is a hugely lifelimiting neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen. Niemann pick disease metabolism a rapidly progressive ar storage disease with progressive neurologic damage due to sphingomyelinase deficiency. Niemannpick disease type c npc, mim 257220 is a neurovisceral lysosomal lipid storage disorder of autosomal recessive inheritance characterized at the cellular level by accumulation of unesterified cholesterol and glycolipids in the endosomallysosomal system patterson et al. Niemannpick disorders are characterized by the buildup of toxic amounts of fatty substances called lipids, specifically sphingolipids and cholesterol, in various. 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 type c npc is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders ataxia, chorea, dystonia, and myoclonus, a vertical supranuclear gaze palsy vsgp, and seizures. 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. 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. Consensus clinical management guidelines for niemannpick. People with this condition experience a build up of lipids in the spleen, liver, lungs, bone marrow, and brain.
Niemann pick disease leads to the irregular and harmful accumulation of fatty substances within various tissues of the body, including liver, spleen, and brain tissue. The authors show that npc1 regulates calcium levels in. The results of a complex analysis of liver tissue are presented four biopsy and two autopsy samples obtained from six patients with niemannpick disease npd with a gross deficiency of sphingomyelinase smase accompanied by a typical increase in sphingomyelin sm. Niemannpick type c npc is a progressive and life limiting autosomal recessive disorder. Mutations in these genes are associated with abnormal endosomallysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. Niemannpick disease metabolism a rapidly progressive ar storage disease with progressive neurologic damage due to sphingomyelinase deficiency. There have been recent developments in testing that make diagnosis easier and new therapies that aim to stabilise the disease process. Niemann pick type c npc disease is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration. However, these patients are now known to have harbored specific alleles of the npc1 locus. The international niemann pick disease registry inpdr is a disease specific patient registry. All of the types of niemann pick disease are autosomal recessive, including. 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. In niemannpick disease, harmful quantities of lipids accumulate in. Free sphingosine levels are much less elevated in brain x3 than in liver or spleen x20 62,64.
Niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage. Niemannpick disease is a condition that affects many body systems. Niemannpick disease information page national institute of. Previously, studies on niemannpick disease were performed on rodents with druginduced enzyme deficiencies, which was less than ideal.
Drugsendocrinologicandmetabolicdrugsadvisorycommitteeucm248677. Niemann pick disease type c npc is a hugely lifelimiting neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen. This presentation is brought to you for free and open access by lvhn scholarly works. Niemannpick type c, npc, guidelines, diagnosis, management. Niemannpick disease the embryo project encyclopedia. Although there are obstacles to be faced, researchers are optimistic that siamese cats will speed the search for a cure or. Npd type a is ar, more common in ashkenazi jews and is characterized by accumulation of excess sphingomyelin and cholesterol in the brain, bm, liver, spleen clinical early infancy onset with feeding problems and delayed or regressing motor development. Niemann pick disease synonyms, niemann pick disease pronunciation, niemann pick disease translation, english dictionary definition of niemann pick disease. Niemannpick type c1 is a lysosomal storage disease caused by mutations in the npc1 gene. Niemannpick disease is an inherited condition involving lipid metabolism, which is the. Jul 12, 2016 expected diseases according to above information 1 gaucher disease 2 tay sachs disease 3 hurlers syndrome 4niemannpick disease further enzymatic and gene studies revealed the presence of niemannpick type a disease. An inherited disorder of lipid metabolism characterized by the accumulation of lipids in the spleen and. Niemannpick type c is an uncommon neurodegenerative lysosomal storage disorder that can cause a progressive neuropsychiatric syndrome associated with supranuclear vertical gaze palsy and a movement disorder.
Niemannpick type c npc disease is a rare genetic disease whose clinical spectrum ranges from a fatal antenatal disorder to an adultonset. Neurological examination 2 years later revealed manual. Npc disease ranges from a neonatal rapidly progressive fatal disorder to an adultonset. Furthermore, there is no uniformity among studies in treatment outcomes or in data analysis and presentation of results. In some affected individuals, haematological defects such as thrombocytopenia low.
These types are classified on the basis of genetic cause and the signs and symptoms of the condition. Niemann pick disease market global industry analysis and. Niemannpick type c npc disease is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration. Mayo clinic doctors are wellacquainted with this complicated disease and are experienced at distinguishing niemannpick from other diseases with similar symptoms. Niemannpick disease type c npc is an autosomal recessive lipid lysosomal. It is an autosomal recessive lysosomal storage disease associated with mutations in npc1 and npc2 genes. Niemannpick disease, type c definition of 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 definition of niemannpick disease by.
Niemannpick disease type b is an inherited condition involving lipid. To reduce the time needed for niemannpick type c npc diagnosis. Niemannpick disease and platelet dysfunction disease. Niemannpick disease with isolated leukemic nonnodal mantle. Niemannpick disease type c2 genetic and rare diseases. The diseas e is caused by deficiency of enzyme, acid sphingomyelinase asm. Dec 20, 2018 niemann pick disease is a group of genetic conditions, which affects the metabolism of fats or lipids in the body. George december 5, 2005 the disease condition involving the breakdown and use of fats and cholesterol in the body harmful amounts of lipids accumulate in the spleen, liver, lungs, bone marrow, and brain autosomal recessive pattern of inheritance two copies of the gene must be present four variants. Niemann pick disease alex gavlin and brad kligman niemann pick is an autosomal recessive genetic disorder resulting in abnormal lipid metabolism. Registered charity number england and wales 1175311. Niemannpick disease type c npc is a fatal neurovisceral lipid storage disease of autosomal inheritance resulting from.
Isabel and toni now lead the niemann pick support groups in spain fundacion niemann pick and the uk niemann pick disease group respectively. Niemannpick 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 c2 is a rare metabolic condition that affects many. Niemannpick disease type b genetic and rare diseases. All of the types of niemannpick disease are autosomal recessive, including. Niemann pick disease is a condition that affects many body systems. Niemannpick disease alex gavlin and brad kligman niemannpick is an autosomal recessive genetic disorder resulting in abnormal lipid metabolism. Niemannpick disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. Although signs and symptoms can develop at any age infancy through adulthood, most affected people develop features of the condition during childhood. In 1914 albert niemann, a german pediatrician who primarily studied infant metabolism, published a description of an ashkenazi jewish infant with jaundice, nervous system and brain impairments, swollen lymph nodes lymphadenopathy, and an enlarged liver and spleen hepatosplenomegaly. Niemannpick type c disease npcd was first described in 1914 and affects approximately 1 in 150 000 live births.
Approximately 50% of cases present before 10 years of age, but manifestations may first be recognized as late as the sixth decade. The international niemannpick disease registry inpdr is a diseasespecific patient registry. Case report 2 an afghan girl was growing normally till 1 year of age. Niemann pick disease is an autosomal recessive disorder that arises due to mutations in the npc 1 or npc 2 gene. The incidence of both niemannpick disease types a and b in all other populations is estimated to be one in 250,000. Niemannpick disease is divided into four main types. Niemann pick disease type c npc is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders ataxia, chorea, dystonia, and myoclonus, a vertical supranuclear gaze palsy vsgp, and seizures. Niemannpick type c npc diseases, caused by mutations in npc1 or npc2, are rare inherited disorders affecting cholesterol metabolism, and are characterised by progressive neurodegeneration and premature death. Niemannpick disease np information cleveland clinic. Np disease encompasses a set of autosomal recessive hereditary abnormalities characterized by the accumulation of lipids, mostly sphingomyelin and cholesterol, in different.
At npuk we are dedicated to supporting the individuals and families affected by these conditions. Albert niemann published the first description of what now is known as niemannpick disease, type a, in 1914. Pick disease, types a and b, are lipid storage disorders caused by complete or partial deficiency of a lysosomal enzyme, acid sphingomyelinase. Niemann pick type c npc is a progressive and life limiting autosomal recessive disorder caused by mutations in either the npc1 or npc2 gene. Niemann pick disease npd, also called sphingomyelincholesterol lipidosis, is a group of autosomal recessive disorders associated with splenomegaly, variable neurologic deficits, and the storage of lipids including sphingomyelin and cholesterol. Mar 27, 2019 niemann pick disease np refers to a group of inherited metabolic disorders known as lipid storage diseases. Niemann pick disease originally was defined in terms of its histology as a reticuloendotheliosis. Niemann pick type c npc diseases, caused by mutations in npc1 or npc2, are rare inherited disorders affecting cholesterol metabolism, and are characterised by progressive neurodegeneration and premature death. In niemann pick disease npd, the incidence for carrier of the genesmpd1, causing asmd, is 1. The three most commonly recognized forms are niemann pick types a and b asmd or acid sphingomyelinase deficiency and niemann pick disease type c npc. Pdf niemann pick disease a case report researchgate. Sanofi genzymenational niemannpick disease foundation, inc.
Niemannpick disease npd is a lipid storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. The adult form of niemannpick disease type c oxford academic. Cyclodextrinnational niemannpick disease foundation, inc. Approximately 95% of cases are caused by mutations in the npc1 gene, referred to as type c1. In this inherited condition, there is deficiency of a lysosomal enzyme called acid sphingomyelinase or disturbance in cholesterol breakdown or transportation.
Information is comprehensive and access is free to all users. Oct 26, 2008 niemann pick type c1 is a lysosomal storage disease caused by mutations in the npc1 gene. There were five cases of npd type a four of them with an atypical, prolonged course and one case of type b. Membership in the nnpdf is free and helps ensure we can keep families. 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 is a group of genetic conditions, which affects the metabolism of fats or lipids in the body. Niemannpick disease is one of a group of lysosomal storage diseases that affect.
Niemannpick 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. Niemann pick disease point mutation mutation free 30. Niemann pick disease is divided into four main types. Niemann pick disease type c nord national organization for. Niemannpick type c disease npc is a childhoodonset neurodegenerative disorder characterized by the accumulation of unesterified cholesterol and glycosphingolipids in late endosomes and lysosomes. Npd type a disease manifests with persistent early jaundice, enlarging abdomen, hepatosplenomegaly, and poor developmental progress and failure to thrive.
Jan 25, 2018 the niemann pick gene mutations are passed from parents to children in a pattern called autosomal recessive inheritance. The clinical spectrum of npc disease ranges from a neonatal rapidly progressive. 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. In niemann pick disease, harmful quantities of lipids accumulate in. 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. It is characterized clinically by diverse symptoms affecting liver, spleen, motor control, and brain. Niemann pick disease is an inherited disease that affects lipid metabolism, or the way fats, lipids, and cholesterol are stored in or removed from your body. A company limited by guarantee and registered in england and wales number 10646129. Each parent has 1 copy of the abnormal gene without having any signs of the disease themselves. Niemann pick np disease is caused by an abnormality in lysosomes, which are unable to degrade macromolecules. The niemann pick gene mutations are passed from parents to children in a pattern called autosomal recessive inheritance. It is associated with poor lysosomal metabolism inclusive of the way lipids are broken down, transported and stored. Jul 19, 2016 niemann pick disease type b is an inherited condition involving lipid metabolism. Niemannpick type c disease lvhn scholarly works lehigh.
Niemannpick type c npc is a lysosomal storage disease associated with mutations in npc1 and npc2 genes. A genetic isolate of niemannpick disease, first identified in patients in colorado and nova scotia, canada, was originally called niemannpick type d npd disease. Isabel and toni now lead the niemannpick support groups in spain fundacion niemannpick and the uk niemannpick disease group respectively. When both parents are carriers, there is a 25% chance that their child will have the disease and a 50% chance that their child will be a carrier. Niemann pick is a progressive disease, and there is no cure. A 54yearold man with niemann pick disease type b with chronic transaminitis, thrombocytopenia, and splenomegaly for 21 years presented with abdominal discomfort. Pdf niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage. Acid sphingomyelinase deficiency asmd disease patients and family community that sanofi genzyme has received fda authorization to begin recruiting for the phase 23 clinical trial of olipudase alfa for adult patients. Expected diseases according to above information 1 gaucher disease 2 tay sachs disease 3 hurlers syndrome 4niemannpick disease further enzymatic and gene studies revealed the presence of niemannpick type a disease. It has been accepted for inclusion in lvhn scholarly works by an authorized administrator. Ninetyfive percent of cases of npc are caused by lossoffunction. 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.
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