U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Niemann-Pick disease, type B

MedGen UID:
78651
Concept ID:
C0268243
Disease or Syndrome
Synonyms: Niemann Pick Disease, Non Neuronopathic Type; Niemann Pick Disease, Type B; Niemann Pick Disease, Visceral; Niemann Pick's Disease Type B; Niemann-Pick Disease, Non-Neuronopathic Type; Niemann-Pick Disease, Type B; Niemann-Pick Disease, Visceral; Niemann-Pick's Disease Type B; Type B Niemann Pick Disease; Type B Niemann-Pick Disease
SNOMED CT: Niemann-Pick disease type B (39390005); Niemann-Pick disease non-neuropathic type (39390005); Niemann-Pick disease, type B (39390005); Niemann-Pick disease, chronic non-neuronopathic (39390005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SMPD1 (11p15.4)
 
Monarch Initiative: MONDO:0011871
OMIM®: 607616
Orphanet: ORPHA77293

Disease characteristics

Excerpted from the GeneReview: Acid Sphingomyelinase Deficiency
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). Enzyme replacement therapy (ERT) is currently FDA approved for the non-central nervous system manifestations of ASMD, regardless of type. As more affected individuals are treated with ERT for longer periods of time, the natural history of ASMD is likely to change. The most common presenting symptom in untreated NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Growth failure typically becomes evident by the second year of life. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. This feature may not be amenable to ERT. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children, although it is unclear if ERT will have an impact on this. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most untreated children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized in untreated individuals by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some central nervous system manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B, even when untreated. [from GeneReviews]
Authors:
Melissa P Wasserstein  |  Edward H Schuchman   view full author information

Additional descriptions

From OMIM
Niemann-Pick disease types A and B are caused by an inherited deficiency of acid sphingomyelinase activity. The clinical phenotype ranges from a severe infantile form with neurologic degeneration resulting in death usually by 3 years of age (type A) to a later-onset nonneurologic form (type B) that is compatible with survival into adulthood. Since intermediate cases also have been reported, the disease is best regarded a single entity with a clinical spectrum (summary by Schuchman, 2007). Schuchman (2007) provided a detailed review of Niemann-Pick disease type B, including clinical management.  http://www.omim.org/entry/607616
From MedlinePlus Genetics
The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). 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. People with Niemann-Pick disease type B usually survive into adulthood.

Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. 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.

Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.  https://medlineplus.gov/genetics/condition/niemann-pick-disease

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Foam cells with lamellar inclusion bodies
MedGen UID:
871121
Concept ID:
C4025590
Finding
The presence of foam cells that contain lamellar inclusion bodies.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Diffuse reticular or finely nodular infiltrations
MedGen UID:
335955
Concept ID:
C1843428
Finding
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Abnormal pulmonary interstitial morphology
MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.
Sea-blue histiocyte syndrome
MedGen UID:
19908
Concept ID:
C0036489
Disease or Syndrome
An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Bone-marrow foam cells
MedGen UID:
383940
Concept ID:
C1856560
Finding
The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance.
Decreased HDL cholesterol concentration
MedGen UID:
57731
Concept ID:
C0151691
Finding
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Decreased acid sphingomyelinase activity
MedGen UID:
375191
Concept ID:
C1843422
Finding
Reduced activity of the enzyme acid sphingomyelinase activity in the blood circulation.
Abnormal macular morphology
MedGen UID:
1624166
Concept ID:
C4520679
Anatomical Abnormality
A structural abnormality of the macula lutea, which is an oval-shaped highly pigmented yellow spot near the center of the retina.

Professional guidelines

PubMed

Lachmann RH, Diaz GA, Wasserstein MP, Armstrong NM, Yarramaneni A, Kim Y, Kumar M
Orphanet J Rare Dis 2023 Apr 25;18(1):94. doi: 10.1186/s13023-023-02700-x. PMID: 37098529Free PMC Article
Maines E, Franceschi R, Rizzardi C, Deodato F, Piccoli G, Gragnaniello V, Burlina A, Soffiati M
J Clin Lipidol 2022 Mar-Apr;16(2):143-154. Epub 2022 Feb 1 doi: 10.1016/j.jacl.2022.01.008. PMID: 35181260
Henderson SL, Packman W, Packman S
Am J Med Genet A 2009 Nov;149A(11):2430-6. doi: 10.1002/ajmg.a.33077. PMID: 19877061

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased acid sphingomyelinase, Acid Sphingomyelinase Deficiency (ASMD), 2022

American College of Medical Genetics and Genomics, Algorithm, Acid Sphingomyelinase Deficiency (ASMD): Decreased Acid Sphingomyelinase (ASM), 2022

Recent clinical studies

Etiology

Cappellini MD, Motta I, Barbato A, Giuffrida G, Manna R, Carubbi F, Giona F
Eur J Intern Med 2023 Feb;108:81-84. Epub 2022 Nov 26 doi: 10.1016/j.ejim.2022.11.028. PMID: 36443133
Liu Y, Luo Y, Xia L, Qiu B, Zhou T, Feng M, Xue F, Chen X, Han L, Zhang J, Xia Q
Liver Transpl 2019 Aug;25(8):1233-1240. Epub 2019 Jun 25 doi: 10.1002/lt.25457. PMID: 30912297
Freitas HMP, Mançano AD, Rodrigues RS, Hochhegger B, Torres PPTES, Escuissato D, Araujo Neto CA, Marchiori E
J Bras Pneumol 2017 Nov-Dec;43(6):451-455. doi: 10.1590/S1806-37562017000000062. PMID: 29340494Free PMC Article
Simões RG, Maia H
BMJ Case Rep 2015 Feb 5;2015 doi: 10.1136/bcr-2014-208286. PMID: 25657196Free PMC Article
McGovern MM, Lippa N, Bagiella E, Schuchman EH, Desnick RJ, Wasserstein MP
Genet Med 2013 Aug;15(8):618-23. Epub 2013 Feb 14 doi: 10.1038/gim.2013.4. PMID: 23412609

Diagnosis

Tirelli C, Rondinone O, Italia M, Mira S, Belmonte LA, De Grassi M, Guido G, Maggioni S, Mondoni M, Miozzo MR, Centanni S
Biomolecules 2024 Feb 11;14(2) doi: 10.3390/biom14020211. PMID: 38397448Free PMC Article
Cesur Baltacı HN, Taşdelen E, Topçu V, Eminoğlu FT, Karabulut HG
J Pediatr Endocrinol Metab 2021 May 26;34(5):653-657. Epub 2021 Feb 26 doi: 10.1515/jpem-2020-0367. PMID: 33647194
Freitas HMP, Mançano AD, Rodrigues RS, Hochhegger B, Torres PPTES, Escuissato D, Araujo Neto CA, Marchiori E
J Bras Pneumol 2017 Nov-Dec;43(6):451-455. doi: 10.1590/S1806-37562017000000062. PMID: 29340494Free PMC Article
Villarrubia J, Velasco-Rodríguez D, Piris-Villaespesa M, Caro M, Méndez G, Vallés A
Br J Haematol 2016 Mar;172(6):840. Epub 2015 Nov 16 doi: 10.1111/bjh.13846. PMID: 26568526
Simões RG, Maia H
BMJ Case Rep 2015 Feb 5;2015 doi: 10.1136/bcr-2014-208286. PMID: 25657196Free PMC Article

Therapy

Zhou ZW, Wang SH, Xu CA, Wu WH, Hui TC, Yin QQ, Zheng W, Pan HY
BMC Med Genomics 2022 Sep 16;15(1):196. doi: 10.1186/s12920-022-01353-2. PMID: 36114502Free PMC Article
Maines E, Franceschi R, Rizzardi C, Deodato F, Piccoli G, Gragnaniello V, Burlina A, Soffiati M
J Clin Lipidol 2022 Mar-Apr;16(2):143-154. Epub 2022 Feb 1 doi: 10.1016/j.jacl.2022.01.008. PMID: 35181260
Ordieres-Ortega L, Galeano-Valle F, Mallén-Pérez M, Muñoz-Delgado C, Apaza-Chavez JE, Menárguez-Palanca FJ, Alvarez-Sala Walther LA, Demelo-Rodríguez P
BMC Med Genet 2020 May 6;21(1):94. doi: 10.1186/s12881-020-01027-9. PMID: 32375665Free PMC Article
Schuchman EH, Wasserstein MP
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:674-81. PMID: 27491215
Schuchman EH
J Inherit Metab Dis 2007 Oct;30(5):654-63. Epub 2007 Jul 12 doi: 10.1007/s10545-007-0632-9. PMID: 17632693

Prognosis

Eskes ECB, Sjouke B, Vaz FM, Goorden SMI, van Kuilenburg ABP, Aerts JMFG, Hollak CEM
Mol Genet Metab 2020 May;130(1):16-26. Epub 2020 Feb 12 doi: 10.1016/j.ymgme.2020.02.002. PMID: 32088119
Liu Y, Luo Y, Xia L, Qiu B, Zhou T, Feng M, Xue F, Chen X, Han L, Zhang J, Xia Q
Liver Transpl 2019 Aug;25(8):1233-1240. Epub 2019 Jun 25 doi: 10.1002/lt.25457. PMID: 30912297
Cassiman D, Packman S, Bembi B, Turkia HB, Al-Sayed M, Schiff M, Imrie J, Mabe P, Takahashi T, Mengel KE, Giugliani R, Cox GF
Mol Genet Metab 2016 Jul;118(3):206-213. Epub 2016 May 11 doi: 10.1016/j.ymgme.2016.05.001. PMID: 27198631
Zampieri S, Filocamo M, Pianta A, Lualdi S, Gort L, Coll MJ, Sinnott R, Geberhiwot T, Bembi B, Dardis A
Hum Mutat 2016 Feb;37(2):139-47. Epub 2015 Dec 1 doi: 10.1002/humu.22923. PMID: 26499107
Simões RG, Maia H
BMJ Case Rep 2015 Feb 5;2015 doi: 10.1136/bcr-2014-208286. PMID: 25657196Free PMC Article

Clinical prediction guides

Eskes ECB, Sjouke B, Vaz FM, Goorden SMI, van Kuilenburg ABP, Aerts JMFG, Hollak CEM
Mol Genet Metab 2020 May;130(1):16-26. Epub 2020 Feb 12 doi: 10.1016/j.ymgme.2020.02.002. PMID: 32088119
Cerón-Rodríguez M, Vázquez-Martínez ER, García-Delgado C, Ortega-Vázquez A, Valencia-Mayoral P, Ramírez-Devars L, Arias-Villegas C, Monroy-Muñoz IE, López M, Cervantes A, Cerbón M, Morán-Barroso VF
Ann Hepatol 2019 Jul-Aug;18(4):613-619. Epub 2019 May 12 doi: 10.1016/j.aohep.2018.12.004. PMID: 31122880
Liu Y, Luo Y, Xia L, Qiu B, Zhou T, Feng M, Xue F, Chen X, Han L, Zhang J, Xia Q
Liver Transpl 2019 Aug;25(8):1233-1240. Epub 2019 Jun 25 doi: 10.1002/lt.25457. PMID: 30912297
Freitas HMP, Mançano AD, Rodrigues RS, Hochhegger B, Torres PPTES, Escuissato D, Araujo Neto CA, Marchiori E
J Bras Pneumol 2017 Nov-Dec;43(6):451-455. doi: 10.1590/S1806-37562017000000062. PMID: 29340494Free PMC Article
Zampieri S, Filocamo M, Pianta A, Lualdi S, Gort L, Coll MJ, Sinnott R, Geberhiwot T, Bembi B, Dardis A
Hum Mutat 2016 Feb;37(2):139-47. Epub 2015 Dec 1 doi: 10.1002/humu.22923. PMID: 26499107

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased acid sphingomyelinase, Acid Sphingomyelinase Deficiency (ASMD), 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Acid Sphingomyelinase Deficiency (ASMD): Decreased Acid Sphingomyelinase (ASM), 2022

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...