When present, fibrosis was periportal and pericellular, predominantly surrounding affected Kupffer cells. Two baseline biopsies exhibited frank cirrhosis. [ncbi.nlm.nih.gov]

• Splenomegaly

  The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. [ncbi.nlm.nih.gov]

  Marked splenomegaly, mild thrombocytopenia and partial respiratory insufficiency existed before this pregnancy. [learningcenter.ehaweb.org]

• Short Stature

  We report a girl with Niemann-Pick disease type B in whom short stature was recorded over a long period. Association of short stature with the presence of a polyglandular involvement in this patient is discussed. [ncbi.nlm.nih.gov]

  Other clinical features include: interstitial lung disease short stature with delayed skeletal maturation ocular abnormalities (cherry red maculae) hyperlipidemia (which can lead to early onset vascular disease) The definitive diagnosis of those diseases [radiopaedia.org]

  stature Delayed bone age Intellectual disabilities Short stature PROGNOSIS Individuals with Niemann-Pick Disease Type A have onset of symptoms such as failing to gain weight and grow appropriately (i.e. failure to thrive) in the first months of life. [evolvegene.com]

  Onset in infancy or childhood Variable phenotype More common in Ashkenazi Jews Allelic disorder to Niemann-Pick disease type A (MIM.257200) short stature (less common) cherry-red maculae (less common) dyspnea frequent respiratory infections decreased [humpath.com]

  Growth restriction and delayed bone age, which can result in significant short stature in adulthood Bone and joint pain Osteopenia (low bone mass) or osteoporosis, which can lead to an increased risk for fractures Delayed onset of puberty (often by several [rarediseases.info.nih.gov]

• Swelling

  This type is quite rare and research on the condition is limited, but the signs and symptoms include swelling of the spleen or brain and neurological problems, such as swelling within the nervous system. [healthline.com]

  Symptoms may include: Abdominal (belly area) swelling within 3 to 6 months Cherry red spot at the back of the eye ( on the retina ) Feeding difficulties Loss of early motor skills (gets worse over time) Type B symptoms are usually milder. [nlm.nih.gov]

  Niemann-Pick disease type C is chronically debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of organs such as the spleen and the liver. [ema.europa.eu]

  Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen) Poor growth Poor weight gain Feeding difficulties Loss of motor skills Diarrhea Vomiting Frequent lung infections Developmental delay In Niemann-Pick disease type [babysfirsttest.org]

• Recurrent Respiratory Infection

  respiratory infections Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ] 0002205 Sea-blue histiocytosis 0001982 Short stature Decreased body height Small [rarediseases.info.nih.gov]

  Although many NPD-B patients are asymptomatic, more severely affected patients may exhibit cough, shortness of breath, and recurrent respiratory infections. 12 Cyanosis, clubbing, rales, and rhonchi may be present on physical examination in such patients [pediatrics.aappublications.org]

  respiratory infections, 17 and some patients develop chronic oxygen dependence with progressive pulmonary failure. 18 The pathophysiology of the pulmonary disease is presumably related to the accumulation of sphingomyelin in the alveolar macrophages, [nature.com]

• Pediatric Disease

  Cyclo to Treat Niemann-Pick Disease Type C Jan 19, 2018: Arimoclomol For NPC Receives Rare Pediatric Disease Designation Dec 06, 2017: CTD Holdings Receives Rare Pediatric Disease Designation for Trappsol Cyclo Sep 28, 2017: CTD Holdings Enrolls First [gii.co.jp]

• Camping

  Despite this background he was evicted from his home by the Nazis and imprisoned in the Theresienstadt Concentration Camp where he died on 3 February 1944 at the age of 76 years. [whonamedit.com]

• Dyspnea

  We report here a unique case of a 55-year-old woman presenting with a clinical picture of Parkinson disease, severe back pain, splenomegaly, and pronounced dyspnea. Radiographic examination of the spine showed multiple vertebral fractures. [ncbi.nlm.nih.gov]

  Onset in infancy or childhood Variable phenotype More common in Ashkenazi Jews Allelic disorder to Niemann-Pick disease type A (MIM.257200) short stature (less common) cherry-red maculae (less common) dyspnea frequent respiratory infections decreased [humpath.com]

  […] spleen cardiovascular calcified atherosclerotic plaques MRI central nervous system pronounced cerebellar and mild supratentorial atrophy skeletal reduced signal in bone marrow 5 Treatment and prognosis Usually, these patients suffer from progressive dyspnea [radiopaedia.org]

  Bone-marrow foam cells 0004333 Decreased HDL cholesterol concentration Decreased circulating high-density lipoprotein cholesterol Decreased HDL cholesterol Low HDL-cholesterol [ more ] 0003233 Diffuse reticular or finely nodular infiltrations 0002207 Dyspnea [rarediseases.info.nih.gov]

  The patient currently continues to be seen at the pulmonology and hepatology outpatient consultations, and he presents intermittent jaundice and maximal exertion dyspnea (MRC scale 0). [archbronconeumol.org]

• Respiratory Insufficiency

  Marked splenomegaly, mild thrombocytopenia and partial respiratory insufficiency existed before this pregnancy. [learningcenter.ehaweb.org]

• Hypertension

  Evaluation showed massive hepatosplenomegaly, infiltration of the liver with Niemann-Pick cells, cirrhosis, and evidence of portal hypertension***. ... In pulmonary artery smooth muscle cells (PASMCs) nicotinic acid adenine ... [proz.com]

  Liver cirrhosis has continued to progress despite the BMT, and haematemesis due to portal hypertension occurred at 17 years of age. [kclpure.kcl.ac.uk]

  Mistry PK, Sirrs S, Chan A, et al Pulmonary hypertension in type 1 Gaucher’s disease: genetic and epigenetic determinants of phenotype and response to therapy. Mol Genet Metab 2002; 77 :91–98. [nature.com]

  Cirrhosis and portal hypertension in a patient with adult Niemann-Pick disease. Gastroenterology. 1991 ; 100 : 567 – 570 Lever AM, Ryder JB. Cor pulmonale in an adult secondary to Niemann-Pick disease. [pediatrics.aappublications.org]

  However, two patients had previously undiagnosed moderate to severe aortic regurgitation and one patient had pulmonary hypertension [ 36 ]. [ojrd.biomedcentral.com]

• Hepatosplenomegaly

  Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no central nervous system signs. [ncbi.nlm.nih.gov]

  The disease is characterized by hepatosplenomegaly during infancy and the majority of patients will develop thrombocytopenia due to hypersplenism. [radiopaedia.org]

  NPD type B has a variable age of presentation but frequently appears early in childhood when hepatosplenomegaly is detected and symptoms of lung involvement may occur. [emedicine.medscape.com]

• Hepatomegaly

  The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. [ncbi.nlm.nih.gov]

  272.7 splenomegaly (cerebroside lipidosis) 272.7 Hepatomegaly (see also Hypertrophy, liver) 789.1 Gaucher's 272.7 Histiocytosis (acute) (chronic) (subacute) 277.89 lipid, lipoid (essential) 272.7 Hyperlipidosis 272.7 hereditary 272.7 Lipidosis 272.7 [icd9data.com]

  Niemann-Pick disease type A (MIM.257200) short stature (less common) cherry-red maculae (less common) dyspnea frequent respiratory infections decreased pulmonary diffusion secondary to alveolar infiltration diffuse reticular or finely nodular infiltrations hepatomegaly [humpath.com]

  Later on, hepatomegaly with developmental delay was observed. Parents also noticed unexplained frequent falls without any sign of seizure. [slideshare.net]

• Liver Fibrosis

  […] and skin pathology Liver fibrosis in almost all patients. [ojrd.biomedcentral.com]

• Neonatal Jaundice

  […] rare disease Niemann-Pick disease type C Disease definition Niemann-Pick disease type C (NP-C) is a lysosomal lipid storage disease (see this term) characterized by variable clinical signs, depending on the age of onset, such as prolonged unexplained neonatal [orpha.net]

• Bone Pain

  Symptoms can include: A progressive enlargement of organs Poor growth Susceptibility to respiratory infections Bleeding problems Bone pain Increased stress on the heart There is usually no neurological involvement in NP-B. [npuk.org]

  [Arthralgia, bone pain, positive antinuclear antibodies and thrombocytopenia...diagnosis: Niemann-Pick disease]. Acta Reumatol Port. 2009 Jan-Mar. 34(1):102-5. [Medline]. Cho YU, Chae JD, Lee WM, et al. [emedicine.medscape.com]

  In general, symptoms include: Anemia (low red blood cell count) Enlarged spleen and liver Easy bleeding and bruising Tiredness Bone pain and fractures Joint pain Eye problems Seizures Krabbe disease: This affects the nervous system. [webmd.com]

• Osteopenia

  […] abnormalities in peripheral blood (decreased HDL-c, increased LDL-c, and hypertriglyceridemia) Plain radiograph chest reticulonodular pattern which usually starts in the lower lobes calcified micronodules skeletal short stature with delayed skeletal maturation osteopenia [radiopaedia.org]

  Growth restriction and delayed bone age, which can result in significant short stature in adulthood Bone and joint pain Osteopenia (low bone mass) or osteoporosis, which can lead to an increased risk for fractures Delayed onset of puberty (often by several [rarediseases.info.nih.gov]

  Other features that have been reported include liver dysfunction, cardiac disease, retinal stigmata, growth retardation, and skeletal manifestations including osteoporosis and osteopenia. 2, 3, 4, 5, 6, 7 In addition, there is a subset of variant patients [nature.com]

  In addition, most adults with NPD B had osteopenia or osteoporosis at one or more sites according to the World Health Organization classification of BMD [ 33 ]. These findings demonstrate that skeletal involvement is a common feature of ASMD. [ojrd.biomedcentral.com]

• Redness of Eye

  All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood. [ghr.nlm.nih.gov]

• Onset in Infancy or Childhood

  Onset in infancy or childhood Variable phenotype More common in Ashkenazi Jews Allelic disorder to Niemann-Pick disease type A (MIM.257200) short stature (less common) cherry-red maculae (less common) dyspnea frequent respiratory infections decreased [humpath.com]

• Neurologic Manifestation

  It is mainly a visceral form without neurologic manifestations despite the massive visceral involvement. [humpath.com]

  The data presented on the repeat-dose safety, pharmacodynamics, and exploratory efficacy of olipudase alfa support its continued development for the investigational use in non-neurological manifestations of ASMD. [news.genzyme.com]

  Type B does not involve major neurological manifestations, unlike type A. Features include frequent respiratory infections and breathing difficulties, as well as enlarged organs including the liver, spleen and kidney. [sema4genomics.com]

  Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: An observational cohort study. [mayoclinic.org]

  Niemann-Pick Type B patients remain mostly free of neurological manifestations and typically live into adulthood. In Niemann-Pick Disease Type B, the defective enzyme retains residual catalytic activity, thus resulting in the milder phenotype. [genedx.com]

• Peripheral Neuropathy

  In patients who live long enough, however, neurologic disorders such as nystagmus, psychiatric disease and peripheral neuropathy may occur. [radiopaedia.org]

  Type B usually occurs in the pre-teen years, with symptoms that include ataxia and peripheral neuropathy. The brain is generally not affected. Other symptoms include enlarged liver and spleen, and pulmonary difficulties. [my.clevelandclinic.org]

  Peripheral neuropathy in type A Niemann-Pick disease. Acta Neuropathol. 63: 66–71 PubMed Google Scholar 21. Labrune, P., Bedossa, P., Huguet, P., Roset, F., Vanier, M. T., and Odièvre, M. 1991. [link.springer.com]

  Neuropathy (ACCPN) [Established Research: Multiple studies with 750+ participants, or scientific consensus] Variant Absent Alpha-1 Antitrypsin Deficiency [Established Research: Multiple studies with 750+ participants, or scientific consensus] Variant [vauva.fi]

  Niemann-Pick type C disease associated with peripheral neuropathy. Pediatr Neurol. 2003; 29 :242–4. [ PubMed : 14629910 ] Zervas M, Somers KL, Thrall MA, Walkley SU. Critical role for glycosphingolipids in Niemann-Pick disease type C. [ncbi.nlm.nih.gov]

• Nystagmus

  In patients who live long enough, however, neurologic disorders such as nystagmus, psychiatric disease and peripheral neuropathy may occur. [radiopaedia.org]

  Vision in the first year of life is likely normal as infants have normal fixation, pupillary reactions, and following movements with no nystagmus. However, by about 2 years of age visual responsiveness may be lost. [disorders.eyes.arizona.edu]

  However, some people with a more severe variant have greater severity of the symptoms above, as well as neurologic features such as ataxia, gross motor delays, learning difficulties, intellectual disabilities, psychiatric disorders, and/or nystagmus. [rarediseases.info.nih.gov]

Papandreou A, Gissen P: Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Therapeutic advances in neurological disorders 2016;9(3):216-229. [rarediseases.org]

• Delayed Bone Age

  bone age Intellectual disabilities Short stature PROGNOSIS Individuals with Niemann-Pick Disease Type A have onset of symptoms such as failing to gain weight and grow appropriately (i.e. failure to thrive) in the first months of life. [evolvegene.com]

  They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. [ghr.nlm.nih.gov]

  Growth restriction and delayed bone age, which can result in significant short stature in adulthood Bone and joint pain Osteopenia (low bone mass) or osteoporosis, which can lead to an increased risk for fractures Delayed onset of puberty (often by several [rarediseases.info.nih.gov]

• Pulmonary Infiltrate

  However, pulmonary infiltration regressed after BMT and there has been no clinical evidence of pulmonary insufficiency. [kclpure.kcl.ac.uk]

  infiltrate (5) mild to severe respiratory disease which can progress to cor pulmonale (6) usually no deterioration in intellect or neurologic status (7) rare patients may show cerebellar ataxia (8) a few patients may have a cherry red or gray granular [meducator3.net]

  In more severely affected type B patients, progressive pulmonary infiltration causes the major disease complications. [ommbid.mhmedical.com]

  In severe cases of type B, progressive pulmonary infiltrates cause major complications. Prenatal screening WBC sphingomyelinase assay Both types are usually suspected by history and examination, most notably hepatosplenomegaly. [merckmanuals.com]

  NPC2: extensive pulmonary infiltration with foam cells, delayed psychomotor development and respiratory failure, with death in early childhood. [patient.info]

• Enlargement of the Liver

  The main features of Niemann-Pick disease type B (NPD-B) are enlargement of the liver and spleen, and mild pulmonary involvement. [ncbi.nlm.nih.gov]

  The disease primarily affects the: liver spleen brain bone marrow This leads to enlargement of the spleen and neurologic problems. The disease is broken down into types A, B, C, and E. [healthline.com]

  The first symptoms of Niemann-Pick Disease Type B (NP-B) are usually an enlarged liver and/or spleen in early childhood. [npuk.org]

  These types of Niemann-Pick disease are characterized by a buildup of fat within cells that leads to lung disease and enlargement of the liver and spleen (hepatosplenomegaly). [ghr.nlm.nih.gov]

• Hypertriglyceridemia

  […] the combination of blood tests and radiological features below is highly suggestive of this diagnosis: interstitial lung disease hepatosplenomegaly with thrombocytopenia lipid abnormalities in peripheral blood (decreased HDL-c, increased LDL-c, and hypertriglyceridemia [radiopaedia.org]

  […] cholesterol Decreased HDL cholesterol Low HDL-cholesterol [ more ] 0003233 Diffuse reticular or finely nodular infiltrations 0002207 Dyspnea Trouble breathing 0002094 Foam cells with lamellar inclusion bodies 0003609 Hepatomegaly Enlarged liver 0002240 Hypertriglyceridemia [rarediseases.info.nih.gov]

• LDL Cholesterol Increased

  LDL cholesterol Increased triglycerides Decreased HDL cholesterol Etiology Caused by mutations in the acid lysosomal sphingomyelin phosphodiesterase-1 gene (SMPD1) (MIM.607608) See also lysosomal storage diseases Niemann-Pick diseases (NPDs) Niemann-Pick [humpath.com]

• Visceromegaly

  Vanier, A new variant of sphingomyelinase deficiency (Niemann‐Pick): visceromegaly, minimal neurological lesions and lowin vivo degradation rate of sphingomyelin, Journal of Inherited Metabolic Disease, 9, 4, (357-366), (1985). A. [doi.org]

• Foam Cell

  The foam cells showed cytoplasm filled with numerous small vacuoles. These findings are typical of type B Niemann-Pick disease (NPD). [imagebank.hematology.org]

  Bone marrow biopsy showed plenty of foam cells and sphingomyelinase level was low, thus conforming our diagnosis. Survival into adulthood and absence of gross neurological involvement suggests Niemann-Pick disease type B. [ncbi.nlm.nih.gov]

  […] and histiocytes in several organs as lung, liver, spleen, kidney. microvacuolated hepatocytes (hepatic microsteatosis) large vacuolated foam cells (’NP cells’) on bone marrow biopsy sea blue histiocytes decreased platelets Clinical synopsis Patients [humpath.com]

Several efficacy end points were identified for future clinical treatment studies. [ncbi.nlm.nih.gov]

There is no specific treatment for Niemann-Pick Disease. Type A is a severe form of disease, with average life span of 18 months. In all other types, treatment is aimed at controlling levels of cholesterol. [jmscr.igmpublication.org]

Treatment No cure exists for Niemann-Pick disease. No effective treatment is available to people with type A or B. For people with mild to moderate type C, a drug called miglustat (Zavesca) may be an option. [mayoclinic.org]

TREATMENT Treatment for Niemann-Pick Disease is symptomatic depending on the features of an individual. [evolvegene.com]

Patients with Niemann-Pick disease type B (NPDB) have a benign course and prognosis. It is mainly a visceral form without neurologic manifestations despite the massive visceral involvement. [humpath.com]

NPD type B is a rare inborn error of metabolism, with a benign course and prognosis, while types A and C are always associated with severe neurological involvement. [ncbi.nlm.nih.gov]

Its onset is usually in late childhood and is much less severe than NPD-A, with a good prognosis of survival into adulthood. [radiopaedia.org]

Prognosis of type C depends on the time of onset of symptoms; the earlier the appearance of symptoms, worse is the prognosis. Patients with late onset of symptoms have survived up to 20 years of age. [medindia.net]

CONCLUSIONS: The presence of macular halos and/or cherry red maculae is not an absolute predictor of neurodegeneration, but should prompt a thorough evaluation to determine the underlying etiology and the precise diagnosis. [ncbi.nlm.nih.gov]

[…] manifestations Associations generalized AL amyloidosis of kappa type ( 7655746 ) Ultrastructure foam cells with lamellar inclusions Laboratory Decreased acid sphingomyelinase activity Increased LDL cholesterol Increased triglycerides Decreased HDL cholesterol Etiology [humpath.com]

Etiology Niemann-Pick disease (NPD) types A and B result from a deficiency of acid sphingomyelinase and lysosomal accumulation of sphingomyelin. [emedicine.medscape.com]

] Type A: death usually occurs by 4 years of age Type B: the earliest diagnosed patients are now middle-aged without neurological impairment Type C: death usually occurs in the late 2nd or 3rd decade (aspiration pneumonia is often the cause) Genetic Etiology [en.wikibooks.org]

Residual acid sphingomyelinase activity in peripheral blood leukocytes is Introduction Clinical definition a lipid storage disorder due to sphingomyelinase deficiency Epidemiology incidence rare, however in Niemann-Pick disease (NPD) type A, it is more [medbullets.com]

[…] lix JS...Monroy Arellano LM 2016 14 Epidemiological, clinical and biochemical characterization of the p. [malacards.org]

Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B. [ncbi.nlm.nih.gov]

Epidemiology Racial differences in incidence Niemann-Pick disease (NPD) is a rare disorder that occurs in persons of all races, [4, 5] although NPD type A is more common in persons of Ashkenazi Jewish descent. [emedicine.medscape.com]

In this study, we investigated the pathophysiology of this HDL deficiency by examining both HDL samples from NPD-B patients and nascent high density lipoprotein (LpA-I) generated by incubation of lipid-free apolipoprotein A-I (apoA-I) with NPD-B fibroblasts [ncbi.nlm.nih.gov]

Other DBs ICD-11: 5C56.0Y ICD-10: E75.2 MeSH: D052536 D052537 OMIM: 257200 607616 Reference PMID: 18567738 Authors Smith EL, Schuchman EH Title The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases. [genome.jp]

The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. Review. Vanier MT, Millat G. Structure and function of the NPC2 protein. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):14-21. Review. [ghr.nlm.nih.gov]

[…] of NPD type A can present as early as 3 months of age type B typically occurs in early childhood location neural tissue (NPD type A) and visceral organs such as the spleen and liver (NPD type A and B); as well as the lung and bone marrow (NPD type B) Pathophysiology [medbullets.com]

When you close your browser window without clicking “sign out”, the site will automatically prevent you from signing in again until your session clears, usually after about 20 minutes. [oed.com]

The NPC2 gene mutations that cause Niemann-Pick disease type C2 reduce or eliminate NPC2 protein activity, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. [ghr.nlm.nih.gov]

Clinical trials Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease. Niemann-Pick care at Mayo Clinic Jan. 25, 2018 References Patterson MC. [mayoclinic.org]

[…] accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 2014 recommending the granting of this designation. the seriousness of the condition; the existence of alternative methods of diagnosis, prevention [ema.europa.eu]