MCID: NMN016
MIFTS: 43

Niemann-Pick Disease, Type B

Categories: Genetic diseases, Neuronal diseases, Respiratory diseases, Metabolic diseases, Rare diseases, Eye diseases, Immune diseases

Aliases & Classifications for Niemann-Pick Disease, Type B

MalaCards integrated aliases for Niemann-Pick Disease, Type B:

Name: Niemann-Pick Disease, Type B 54 29 13 42 69
Niemann-Pick Disease Type E 56 71
Niemann-Pick Disease Intermediate with Visceral Involvement and Rapid Progression 71
Niemann-Pick Disease Adult Non-Neuronopathic Form 71
Niemann-Pick Disease Visceral Form 71
Niemann-Pick Disease, Type a 69
Niemann-Picks Disease Type B 52
Niemann-Pick Disease, Type E 69
Niemann-Pick Disease Type B 56
Sphingomyelinase Deficiency 71
Niemann-Pick Disease Type I 71
Niemann-Pick Disease Type F 71
Sphingomyelin Lipidosis 71
Niemann-Pick Disease B 71
Niemann-Pick Diseases 69
Npdb 71
Npb 71

Characteristics:

Orphanet epidemiological data:

56
niemann-pick disease type b
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: young Adult;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
onset in infancy or childhood
more common in ashkenazi jews
allelic disorder to niemann-pick disease type a


HPO:

32
niemann-pick disease, type b:
Onset and clinical course phenotypic variability juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 607616
MESH via Orphanet 43 D052537
UMLS via Orphanet 70 C0268243 C0268248
ICD10 via Orphanet 34 E75.2
MeSH 42 D052537

Summaries for Niemann-Pick Disease, Type B

UniProtKB/Swiss-Prot : 71 Niemann-Pick disease B: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood.

MalaCards based summary : Niemann-Pick Disease, Type B, also known as niemann-pick disease type e, is related to niemann-pick disease and niemann-pick disease, type a, and has symptoms including short stature, recurrent respiratory infections and hypertriglyceridemia. An important gene associated with Niemann-Pick Disease, Type B is SMPD1 (Sphingomyelin Phosphodiesterase 1). The drugs alemtuzumab and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and lung.

OMIM : 54
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. (607616)

Related Diseases for Niemann-Pick Disease, Type B

Diseases in the Niemann-Pick Disease family:

Niemann-Pick Disease, Type a Niemann-Pick Disease, Type B
Niemann-Pick Disease, Type C2 Niemann-Pick Disease, Type C1

Diseases related to Niemann-Pick Disease, Type B via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
id Related Disease Score Top Affiliating Genes
1 niemann-pick disease 11.9
2 niemann-pick disease, type a 11.2
3 pick disease 10.8
4 acid sphingomyelinase deficiency 10.2
5 histiocytosis 10.1
6 pulmonary alveolar proteinosis 10.0
7 interstitial lung disease 10.0
8 myositis 10.0
9 myositis ossificans 10.0
10 lung disease 10.0
11 lichen nitidus 10.0
12 coronary artery disease 10.0
13 hematopoietic stem cell transplantation 10.0
14 hepatitis 10.0
15 thrombocytopenia 10.0
16 artery disease 10.0

Graphical network of the top 20 diseases related to Niemann-Pick Disease, Type B:



Diseases related to Niemann-Pick Disease, Type B

Symptoms & Phenotypes for Niemann-Pick Disease, Type B

Symptoms via clinical synopsis from OMIM:

54

Abdomen- Liver:
hepatomegaly

Respiratory- Lung:
dyspnea
frequent respiratory infections
diffuse reticular or finely nodular infiltrations
decreased pulmonary diffusion secondary to alveolar infiltration

Growth- Height:
short stature (less common)

Head And Neck- Eyes:
cherry-red maculae (less common)

Abdomen- Spleen:
splenomegaly

Laboratory- Abnormalities:
decreased hdl cholesterol
increased triglycerides
electron microscopy of foam cells shows lamellar inclusions
decreased acid sphingomyelinase activity
multiple visceral organs (lung, liver, spleen, kidney) contain foamy resident cells and histiocytes
more
Hematology:
large vacuolated foam cells ('np cells') on bone marrow biopsy
'sea blue' histiocytes
decreased platelets

Neurologic- Central Nervous System:
absence of neurologic manifestations


Clinical features from OMIM:

607616

Human phenotypes related to Niemann-Pick Disease, Type B:

32 (show all 13)
id Description HPO Frequency HPO Source Accession
1 short stature 32 HP:0004322
2 recurrent respiratory infections 32 HP:0002205
3 hypertriglyceridemia 32 HP:0002155
4 hepatomegaly 32 HP:0002240
5 splenomegaly 32 HP:0001744
6 dyspnea 32 HP:0002094
7 diffuse reticular or finely nodular infiltrations 32 HP:0002207
8 hypoalphalipoproteinemia 32 HP:0003233
9 abnormality of the macula 32 HP:0001103
10 sea-blue histiocytosis 32 HP:0001982
11 bone-marrow foam cells 32 HP:0004333
12 hyperbetalipoproteinemia 32 HP:0003141
13 foam cells with lamellar inclusion bodies 32 HP:0003609

UMLS symptoms related to Niemann-Pick Disease, Type B:


constipation, vomiting, muscle weakness, dyspnea

Drugs & Therapeutics for Niemann-Pick Disease, Type B

Drugs for Niemann-Pick Disease, Type B (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational Phase 2 216503-57-0
2
Busulfan Approved, Investigational Phase 2 55-98-1 2478
3
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
4 Alkylating Agents Phase 2
5 Antirheumatic Agents Phase 2
6 Immunosuppressive Agents Phase 2
7
Betadex Experimental Phase 1 7585-39-9 320761

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Study of VTS-270 (2-hydroxypropyl-β-cyclodextrin) to Treat Niemann-Pick Type C1 (NPC1) Disease Active, not recruiting NCT02534844 Phase 2, Phase 3 VTS-270;Sham Procedure Control
2 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
3 Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease Completed NCT01747135 Phase 1 VTS-270

Search NIH Clinical Center for Niemann-Pick Disease, Type B

Cochrane evidence based reviews: niemann-pick disease, type b

Genetic Tests for Niemann-Pick Disease, Type B

Genetic tests related to Niemann-Pick Disease, Type B:

id Genetic test Affiliating Genes
1 Niemann-Pick Disease, Type B 29
2 Niemann-Pick Disease Type B 24 SMPD1

Anatomical Context for Niemann-Pick Disease, Type B

MalaCards organs/tissues related to Niemann-Pick Disease, Type B:

39
Bone, Bone Marrow, Lung, Liver, Kidney, Spleen, Skin

Publications for Niemann-Pick Disease, Type B

Articles related to Niemann-Pick Disease, Type B:

(show all 47)
id Title Authors Year
1
Interstitial Lung Disease Associated with Adult Niemann-Pick Disease Type B. ( 28601876 )
2017
2
Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination. ( 27408787 )
2016
3
Niemann-Pick Disease Type B in a 21 Year Old Male. ( 27277377 )
2016
4
Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases. ( 27198631 )
2016
5
Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B. ( 25920558 )
2015
6
Novel first-dose adverse drug reactions during a phase I trial of olipudase alfa (recombinant human acid sphingomyelinase) in adults with Niemann-Pick disease type B (acid sphingomyelinase deficiency). ( 25834946 )
2015
7
Adult Niemann-Pick disease type B with myositis ossificans: a case report. ( 26338042 )
2015
8
A novel missense SMPD1 gene mutation, T460P, and clinical findings in a patient with Niemann-Pick disease type B presenting to a lipid disorders clinic. ( 24643943 )
2014
9
Generalized lichen nitidus in a boy with Niemann-Pick disease type B. ( 24474110 )
2013
10
Cholesterol trapping in Niemann-Pick disease type B fibroblasts can be relieved by expressing the phosphotyrosine binding domain of GULP. ( 23415435 )
2013
11
Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B. ( 22718274 )
2013
12
Liver and skin histopathology in adults with acid sphingomyelinase deficiency (Niemann-Pick disease type B). ( 22613999 )
2012
13
Lung affectation in an adult patient with Niemann-Pick disease, type B. ( 22075404 )
2012
14
Adult-onset pulmonary involvement in Niemann-Pick disease type B. ( 22462311 )
2011
15
Imaging manifestations of Niemann-Pick disease type B. ( 20028884 )
2010
16
Diagnostic and predictive methods for a Niemann-Pick disease type B patient with ocular involvement. ( 20585986 )
2010
17
Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis. ( 19864213 )
2009
18
Niemann-Pick disease type B with severe coronary artery disease and early recurrence after coronary artery bypass grafting. ( 21291790 )
2009
19
Psychosocial aspects of patients with Niemann-Pick disease, type B. ( 19877061 )
2009
20
Niemann-Pick disease type B presenting with hepatosplenomegaly and thrombocytopenia. ( 19088546 )
2008
21
A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. ( 18625664 )
2008
22
Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B. ( 16319418 )
2006
23
Clinical findings in Niemann-Pick disease type B. ( 16472269 )
2006
24
Treatment of hyperlipidemia associated with Niemann-Pick disease type B by fenofibrate. ( 16211396 )
2006
25
ESI-MS quantitation of increased sphingomyelin in Niemann-Pick disease type B HDL. ( 15741650 )
2005
26
Successful hematopoietic stem cell transplantation for Niemann-Pick disease type B. ( 16199719 )
2005
27
A very unusual presentation of Niemann-Pick disease type B in an infant: similar findings to congenital lobar emphysema. ( 16163596 )
2005
28
Ocular manifestations of Niemann-Pick disease type B. ( 15234149 )
2004
29
Preimplantation genetic diagnosis for Niemann-Pick disease type B. ( 15612058 )
2004
30
The R608del mutation in the acid sphingomyelinase gene (SMPD1) is the most prevalent among patients from Gran Canaria Island with Niemann-Pick disease type B. ( 12694237 )
2003
31
Niemann-Pick disease type B: an unusual clinical presentation with multiple vertebral fractures. ( 11932991 )
2002
32
Sea-blue histiocytes in bone marrow of patient with Niemann-Pick disease type B. ( 11524264 )
2001
33
Hepatic storage of glycogen in Niemann-Pick disease type B. ( 11391349 )
2001
34
Sea-blue histiocytosis secondary to Niemann-Pick disease type B: a case report. ( 11732877 )
2001
35
Niemann-Pick disease type B in pregnancy. ( 9166354 )
1997
36
Asymptomatic pulmonary involvement in 2 children with Niemann-Pick disease type B. ( 8177975 )
1994
37
Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa. ( 8225311 )
1993
38
Niemann-Pick disease type B with ocular involvement: report of a case. ( 1776442 )
1991
39
Fatal liver failure in two children with Niemann-Pick disease type B. ( 1919942 )
1991
40
Evidence of polyglandular involvement in Niemann-Pick disease type B. ( 2820735 )
1987
41
Treatment of Niemann-Pick disease type B by allogeneic bone marrow transplantation. ( 3121020 )
1987
42
Niemann-Pick disease type B: clinical signs and follow-up of a new case. ( 3088327 )
1986
43
Ocular involvement in Niemann-Pick disease type B. ( 3958834 )
1986
44
Niemann-Pick disease type B: first-trimester prenatal diagnosis on chorionic villi and biochemical study of a foetus at 12 weeks of development. ( 3933867 )
1985
45
Ultrastructural investigations on two lymphoid cell lines from Niemann-Pick disease type B. ( 6087964 )
1984
46
Niemann Pick disease type B with oculoneural involvement. ( 6418652 )
1983
47
A report of a patient with Niemann-Pick disease type B and a review of the patients in Japan. ( 7334690 )
1981

Variations for Niemann-Pick Disease, Type B

UniProtKB/Swiss-Prot genetic disease variations for Niemann-Pick Disease, Type B:

71 (show top 50) (show all 65)
id Symbol AA change Variation ID SNP ID
1 SMPD1 p.Gly242Arg VAR_005058
2 SMPD1 p.Glu246Gln VAR_005059
3 SMPD1 p.Met382Ile VAR_005061
4 SMPD1 p.Asn383Ser VAR_005062
5 SMPD1 p.Trp391Gly VAR_005064
6 SMPD1 p.Ser436Arg VAR_005065
7 SMPD1 p.Cys157Arg VAR_011387
8 SMPD1 p.Ser248Arg VAR_015287
9 SMPD1 p.Pro371Ser VAR_015289
10 SMPD1 p.His421Tyr VAR_015290
11 SMPD1 p.Pro475Leu VAR_015292
12 SMPD1 p.Cys92Trp VAR_060871
13 SMPD1 p.Leu103Pro VAR_060872
14 SMPD1 p.Val130Ala VAR_060873
15 SMPD1 p.Leu137Pro VAR_060874
16 SMPD1 p.Gly166Arg VAR_060875
17 SMPD1 p.Ile176Asn VAR_060876
18 SMPD1 p.Ala196Pro VAR_060878
19 SMPD1 p.Arg200Cys VAR_060879
20 SMPD1 p.Leu225Met VAR_060880
21 SMPD1 p.Leu225Pro VAR_060881
22 SMPD1 p.Arg228Cys VAR_060882
23 SMPD1 p.Gly232Asp VAR_060884
24 SMPD1 p.Trp244Cys VAR_060886
25 SMPD1 p.Gly245Ser VAR_060887
26 SMPD1 p.Ala281Thr VAR_060891
27 SMPD1 p.Pro323Ala VAR_060896
28 SMPD1 p.Pro330Arg VAR_060897
29 SMPD1 p.Ala357Asp VAR_060899
30 SMPD1 p.Arg376His VAR_060901
31 SMPD1 p.Arg376Leu VAR_060902
32 SMPD1 p.Ser379Pro VAR_060903
33 SMPD1 p.Ala413Val VAR_060905
34 SMPD1 p.Cys431Arg VAR_060907
35 SMPD1 p.Leu432Pro VAR_060908
36 SMPD1 p.Trp435Cys VAR_060909
37 SMPD1 p.Ala452Val VAR_060911
38 SMPD1 p.Gly456Asp VAR_060912
39 SMPD1 p.Arg474Trp VAR_060914
40 SMPD1 p.Phe480Leu VAR_060915
41 SMPD1 p.Thr486Ala VAR_060918
42 SMPD1 p.Tyr488Asn VAR_060919
43 SMPD1 p.Gly494Ser VAR_060920
44 SMPD1 p.Arg496Cys VAR_060921
45 SMPD1 p.His514Gln VAR_060924
46 SMPD1 p.Glu515Val VAR_060925
47 SMPD1 p.Trp533Arg VAR_060927
48 SMPD1 p.Leu549Pro VAR_060928
49 SMPD1 p.Asp563Tyr VAR_060929
50 SMPD1 p.Lys576Asn VAR_060930

ClinVar genetic disease variations for Niemann-Pick Disease, Type B:

6 (show all 23)
id Gene Variation Type Significance SNP ID Assembly Location
1 SMPD1 NM_000543.4(SMPD1): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs120074117 GRCh37 Chromosome 11, 6415434: 6415434
2 SMPD1 NM_000543.4(SMPD1): c.1314C> A (p.Ser438Arg) single nucleotide variant Pathogenic rs267607073 GRCh37 Chromosome 11, 6414897: 6414897
3 SMPD1 NM_000543.4(SMPD1): c.730G> A (p.Gly244Arg) single nucleotide variant Pathogenic rs120074122 GRCh37 Chromosome 11, 6413025: 6413025
4 SMPD1 NM_000543.4(SMPD1): c.1154A> G (p.Asn385Ser) single nucleotide variant Pathogenic rs120074123 GRCh37 Chromosome 11, 6414508: 6414508
5 SMPD1 NM_000543.4(SMPD1): c.911T> C (p.Leu304Pro) single nucleotide variant Pathogenic rs120074124 GRCh37 Chromosome 11, 6413206: 6413206
6 SMPD1 NM_000543.4(SMPD1): c.1267C> T (p.His423Tyr) single nucleotide variant Pathogenic rs120074126 GRCh37 Chromosome 11, 6414850: 6414850
7 SMPD1 NM_000543.4(SMPD1): c.1327C> T (p.Arg443Ter) single nucleotide variant Pathogenic rs120074127 GRCh37 Chromosome 11, 6414910: 6414910
8 SMPD1 NM_000543.4(SMPD1): c.880C> A (p.Gln294Lys) single nucleotide variant Pathogenic rs120074128 GRCh37 Chromosome 11, 6413175: 6413175
9 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh37 Chromosome 11, 6414445: 6414445
10 SMPD1 NM_000543.4(SMPD1): c.1299T> G (p.Cys433Trp) single nucleotide variant Likely pathogenic rs398123475 GRCh37 Chromosome 11, 6414882: 6414882
11 SMPD1 NM_000543.4(SMPD1): c.1420_1421delCT (p.Leu474Glufs) deletion Pathogenic rs398123476 GRCh37 Chromosome 11, 6415205: 6415206
12 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh37 Chromosome 11, 6415211: 6415211
13 SMPD1 NM_000543.4(SMPD1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs398123478 GRCh37 Chromosome 11, 6415565: 6415565
14 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic rs398123479 GRCh37 Chromosome 11, 6413052: 6413052
15 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh37 Chromosome 11, 6413137: 6413144
16 SMPD1 NM_000543.4(SMPD1): c.1493G> A (p.Arg498His) single nucleotide variant Likely pathogenic rs120074117 GRCh37 Chromosome 11, 6415434: 6415434
17 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic rs727504166 GRCh38 Chromosome 11, 6391540: 6391540
18 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh37 Chromosome 11, 6412649: 6412649
19 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh37 Chromosome 11, 6412868: 6412868
20 SMPD1 NM_000543.4(SMPD1): c.785_807del23 (p.Leu262Argfs) deletion Pathogenic rs794727252 GRCh37 Chromosome 11, 6413080: 6413102
21 SMPD1 NM_000543.4(SMPD1): c.558_559insT (p.Pro187Serfs) insertion Pathogenic rs756366019 GRCh37 Chromosome 11, 6412853: 6412854
22 SMPD1 NM_000543.4(SMPD1): c.1829_1831delGCC (p.Arg610del) deletion Pathogenic rs120074118 GRCh37 Chromosome 11, 6415770: 6415772
23 SMPD1 NM_000543.4(SMPD1): c.1492C> T (p.Arg498Cys) single nucleotide variant Likely pathogenic rs769904764 GRCh37 Chromosome 11, 6415433: 6415433

Expression for Niemann-Pick Disease, Type B

Search GEO for disease gene expression data for Niemann-Pick Disease, Type B.

Pathways for Niemann-Pick Disease, Type B

GO Terms for Niemann-Pick Disease, Type B

Sources for Niemann-Pick Disease, Type B

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....