MCID: NMN016
MIFTS: 42

Niemann-Pick Disease, Type B

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

Aliases & Classifications for Niemann-Pick Disease, Type B

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

Name: Niemann-Pick Disease, Type B 53 28 13 41 69
Niemann-Pick Disease Type E 55 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 51
Niemann-Pick Disease, Type E 69
Sphingomyelinase Deficiency 71
Niemann-Pick Disease Type B 55
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:

55
niemann-pick disease type b
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: young Adult;

OMIM:

53
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:

31
niemann-pick disease, type b:
Onset and clinical course phenotypic variability juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 607616
MESH via Orphanet 42 D052537
UMLS via Orphanet 70 C0268243 C0268248
ICD10 via Orphanet 33 E75.2
MeSH 41 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 dyspnea, splenomegaly and recurrent respiratory infections. An important gene associated with Niemann-Pick Disease, Type B is SMPD1 (Sphingomyelin Phosphodiesterase 1). The drugs Cyclophosphamide and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and lung.

OMIM : 53 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 C1
Niemann-Pick Disease, Type B Niemann-Pick Disease, Type C2

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

(show all 19)
# Related Disease Score Top Affiliating Genes
1 niemann-pick disease 12.0
2 niemann-pick disease, type a 11.3
3 body mass index quantitative trait locus 11 11.1
4 acid sphingomyelinase deficiency 10.3
5 sea-blue histiocyte disease 10.2
6 hematopoietic stem cell transplantation 10.2
7 histiocytosis 10.2
8 arteries, anomalies of 10.0
9 emphysema, congenital lobar 10.0
10 myositis 10.0
11 infantile liver failure syndrome 1 10.0
12 coronary artery anomaly 10.0
13 hepatitis 10.0
14 thrombocytopenia 10.0
15 pulmonary alveolar proteinosis 10.0
16 interstitial lung disease 10.0
17 myositis ossificans 10.0
18 lung disease 10.0
19 lichen nitidus 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:

53
Respiratory Lung:
dyspnea
diffuse reticular or finely nodular infiltrations
frequent respiratory infections
decreased pulmonary diffusion secondary to alveolar infiltration

Abdomen Liver:
hepatomegaly

Growth Height:
short stature (less common)

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

Abdomen Spleen:
splenomegaly

Laboratory Abnormalities:
decreased hdl cholesterol
electron microscopy of foam cells shows lamellar inclusions
increased triglycerides
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:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 dyspnea 31 HP:0002094
2 splenomegaly 31 HP:0001744
3 recurrent respiratory infections 31 HP:0002205
4 hepatomegaly 31 HP:0002240
5 short stature 31 HP:0004322
6 hypertriglyceridemia 31 HP:0002155
7 diffuse reticular or finely nodular infiltrations 31 HP:0002207
8 sea-blue histiocytosis 31 HP:0001982
9 bone-marrow foam cells 31 HP:0004333
10 decreased circulating high-density lipoprotein levels 31 HP:0003233
11 increased circulating low-density lipoprotein levels 31 HP:0003141
12 foam cells with lamellar inclusion bodies 31 HP:0003609
13 abnormal macular morphology 31 HP:0001103

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


dyspnea, muscle weakness, vomiting, constipation

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 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
2
Busulfan Approved, Investigational Phase 2 55-98-1 2478
3
alemtuzumab Approved, Investigational Phase 2 216503-57-0
4 Alkylating Agents Phase 2
5 Immunosuppressive Agents Phase 2
6 Antirheumatic Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan

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:

# Genetic test Affiliating Genes
1 Niemann-Pick Disease, Type B 28 SMPD1

Anatomical Context for Niemann-Pick Disease, Type B

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

38
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 50)
# Title Authors Year
1
Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity. ( 29090525 )
2018
2
Interstitial Lung Disease Associated with Adult Niemann-Pick Disease Type B. ( 28601876 )
2017
3
Corrigendum to "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" [Mol. Genet. Metab. 118 (2016) 206-213]. ( 29129654 )
2017
4
Niemann-Pick disease type B: HRCT assessment of pulmonary involvement. ( 29340494 )
2017
5
Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination. ( 27408787 )
2016
6
Niemann-Pick Disease Type B in a 21 Year Old Male. ( 27277377 )
2016
7
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
8
Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B. ( 25920558 )
2015
9
Adult Niemann-Pick disease type B with myositis ossificans: a case report. ( 26338042 )
2015
10
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
11
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
12
Generalized lichen nitidus in a boy with Niemann-Pick disease type B. ( 24474110 )
2013
13
Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B. ( 22718274 )
2013
14
Cholesterol trapping in Niemann-Pick disease type B fibroblasts can be relieved by expressing the phosphotyrosine binding domain of GULP. ( 23415435 )
2013
15
Liver and skin histopathology in adults with acid sphingomyelinase deficiency (Niemann-Pick disease type B). ( 22613999 )
2012
16
Lung affectation in an adult patient with Niemann-Pick disease, type B. ( 22075404 )
2012
17
Adult-onset pulmonary involvement in Niemann-Pick disease type B. ( 22462311 )
2011
18
Imaging manifestations of Niemann-Pick disease type B. ( 20028884 )
2010
19
Diagnostic and predictive methods for a Niemann-Pick disease type B patient with ocular involvement. ( 20585986 )
2010
20
Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis. ( 19864213 )
2009
21
Niemann-Pick disease type B with severe coronary artery disease and early recurrence after coronary artery bypass grafting. ( 21291790 )
2009
22
Psychosocial aspects of patients with Niemann-Pick disease, type B. ( 19877061 )
2009
23
Niemann-Pick disease type B presenting with hepatosplenomegaly and thrombocytopenia. ( 19088546 )
2008
24
A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. ( 18625664 )
2008
25
Treatment of hyperlipidemia associated with Niemann-Pick disease type B by fenofibrate. ( 16211396 )
2006
26
Clinical findings in Niemann-Pick disease type B. ( 16472269 )
2006
27
Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B. ( 16319418 )
2006
28
ESI-MS quantitation of increased sphingomyelin in Niemann-Pick disease type B HDL. ( 15741650 )
2005
29
Successful hematopoietic stem cell transplantation for Niemann-Pick disease type B. ( 16199719 )
2005
30
A very unusual presentation of Niemann-Pick disease type B in an infant: similar findings to congenital lobar emphysema. ( 16163596 )
2005
31
Preimplantation genetic diagnosis for Niemann-Pick disease type B. ( 15612058 )
2004
32
Ocular manifestations of Niemann-Pick disease type B. ( 15234149 )
2004
33
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
34
Niemann-Pick disease type B: an unusual clinical presentation with multiple vertebral fractures. ( 11932991 )
2002
35
Sea-blue histiocytes in bone marrow of patient with Niemann-Pick disease type B. ( 11524264 )
2001
36
Sea-blue histiocytosis secondary to Niemann-Pick disease type B: a case report. ( 11732877 )
2001
37
Hepatic storage of glycogen in Niemann-Pick disease type B. ( 11391349 )
2001
38
Niemann-Pick disease type B in pregnancy. ( 9166354 )
1997
39
Asymptomatic pulmonary involvement in 2 children with Niemann-Pick disease type B. ( 8177975 )
1994
40
Deletion of arginine (608) in acid sphingomyelinase is the prevalent mutation among Niemann-Pick disease type B patients from northern Africa. ( 8225311 )
1993
41
Fatal liver failure in two children with Niemann-Pick disease type B. ( 1919942 )
1991
42
Niemann-Pick disease type B with ocular involvement: report of a case. ( 1776442 )
1991
43
Evidence of polyglandular involvement in Niemann-Pick disease type B. ( 2820735 )
1987
44
Treatment of Niemann-Pick disease type B by allogeneic bone marrow transplantation. ( 3121020 )
1987
45
Ocular involvement in Niemann-Pick disease type B. ( 3958834 )
1986
46
Niemann-Pick disease type B: clinical signs and follow-up of a new case. ( 3088327 )
1986
47
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
48
Ultrastructural investigations on two lymphoid cell lines from Niemann-Pick disease type B. ( 6087964 )
1984
49
Niemann Pick disease type B with oculoneural involvement. ( 6418652 )
1983
50
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)
# 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)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh37 Chromosome 11, 6414445: 6414445
2 SMPD1 NM_000543.4(SMPD1): c.1299T> G (p.Cys433Trp) single nucleotide variant Likely pathogenic rs398123475 GRCh37 Chromosome 11, 6414882: 6414882
3 SMPD1 NM_000543.4(SMPD1): c.1420_1421delCT (p.Leu474Glufs) deletion Pathogenic rs398123476 GRCh37 Chromosome 11, 6415205: 6415206
4 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh37 Chromosome 11, 6415211: 6415211
5 SMPD1 NM_000543.4(SMPD1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs398123478 GRCh37 Chromosome 11, 6415565: 6415565
6 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic rs398123479 GRCh37 Chromosome 11, 6413052: 6413052
7 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh37 Chromosome 11, 6413137: 6413144
8 SMPD1 NM_000543.4(SMPD1): c.1493G> A (p.Arg498His) single nucleotide variant Likely pathogenic rs120074117 GRCh37 Chromosome 11, 6415434: 6415434
9 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic rs727504166 GRCh38 Chromosome 11, 6391540: 6391540
10 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh37 Chromosome 11, 6412649: 6412649
11 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh37 Chromosome 11, 6412868: 6412868
12 SMPD1 NM_000543.4(SMPD1): c.785_807del23 (p.Leu262Argfs) deletion Pathogenic rs794727252 GRCh37 Chromosome 11, 6413080: 6413102
13 SMPD1 NM_000543.4(SMPD1): c.558_559insT (p.Pro187Serfs) insertion Pathogenic rs756366019 GRCh37 Chromosome 11, 6412853: 6412854
14 SMPD1 NM_000543.4(SMPD1): c.1829_1831delGCC (p.Arg610del) deletion Pathogenic rs120074118 GRCh37 Chromosome 11, 6415770: 6415772
15 SMPD1 NM_000543.4(SMPD1): c.1492C> T (p.Arg498Cys) single nucleotide variant Likely pathogenic rs769904764 GRCh37 Chromosome 11, 6415433: 6415433
16 SMPD1 NM_000543.4(SMPD1): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs120074117 GRCh37 Chromosome 11, 6415434: 6415434
17 SMPD1 NM_000543.4(SMPD1): c.1314C> A (p.Ser438Arg) single nucleotide variant Pathogenic rs267607073 GRCh37 Chromosome 11, 6414897: 6414897
18 SMPD1 NM_000543.4(SMPD1): c.730G> A (p.Gly244Arg) single nucleotide variant Pathogenic rs120074122 GRCh37 Chromosome 11, 6413025: 6413025
19 SMPD1 NM_000543.4(SMPD1): c.1154A> G (p.Asn385Ser) single nucleotide variant Pathogenic rs120074123 GRCh37 Chromosome 11, 6414508: 6414508
20 SMPD1 NM_000543.4(SMPD1): c.911T> C (p.Leu304Pro) single nucleotide variant Pathogenic rs120074124 GRCh37 Chromosome 11, 6413206: 6413206
21 SMPD1 NM_000543.4(SMPD1): c.1267C> T (p.His423Tyr) single nucleotide variant Pathogenic rs120074126 GRCh37 Chromosome 11, 6414850: 6414850
22 SMPD1 NM_000543.4(SMPD1): c.1327C> T (p.Arg443Ter) single nucleotide variant Pathogenic rs120074127 GRCh37 Chromosome 11, 6414910: 6414910
23 SMPD1 NM_000543.4(SMPD1): c.880C> A (p.Gln294Lys) single nucleotide variant Pathogenic rs120074128 GRCh37 Chromosome 11, 6413175: 6413175

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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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