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

The patient currently follows no type of treatment and only presents pulmonary and hepatic affectation with no central nervous system affectation. [archbronconeumol.org]

• 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]

• Recurrent Respiratory Infections

  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]

• 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]

  […] 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]

  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]

  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]

  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]

• 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]

  On physical examination, minimal bibasilar crackles, subconjunctival jaundice and hepatosplenomegaly are observed. Neurological examination is normal. [archbronconeumol.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]

• 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]

• 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]

  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]

  neuropathy. 8, 9 Accompanying this marked phenotypic variability among patients with NP-B is a broad range of disease severity. [nature.com]

• 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]

• Reticulonodular Pattern

  pattern which usually starts in the lower lobes calcified micronodules skeletal short stature with delayed skeletal maturation osteopenia CT chest smooth interlobular and intralobular septal thickening patchy ground-glass attenuation (can form " crazy [radiopaedia.org]

  […] is abnormal in half of the patients. 3 The radiological findings are determined by the existence of reticulonodular pattern with thickening of the interlobular septa, ground glass opacities and sometimes millimetric nodules that may be calcified. 2,8,10 [archbronconeumol.org]

• 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]

• Triglycerides Decreased

  […] acid sphingomyelinase activity 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 [humpath.com]

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

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

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, Diagnosis, and Screening Currently there is no treatment for Niemann-Pick Type A disease (NPA). Approximately 1,200 Type A & B cases have been diagnosed world wide. [niemann-pickdisease.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]

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]

[…] 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]

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]

The development of enzyme replacement and gene therapies might also be helpful for those with type B. restricting one's diet does not prevent the buildup of lipids in cells and tissues. What is the prognosis? Infants with type A die in infancy. [my.clevelandclinic.org]