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MCID: NMN013
MIFTS: 59

Niemann-Pick Disease, Type a

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Metabolic diseases, Immune diseases, Respiratory diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Niemann-Pick Disease, Type a

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

Name: Niemann-Pick Disease, Type a 57 29 13 6 44 40 73
Sphingomyelinase Deficiency 57 53 75
Niemann-Pick Disease Type a 12 53 59
Sphingomyelin Lipidosis 57 53 75
Niemann-Pick Disease, Intermediate, Protracted Neurovisceral 29 6
Niemann-Pick Disease Intermediate Protracted Neurovisceral 75
Niemann-Pick Disease Acute Neuronopathic Form 75
Niemann-Pick Disease Acute Neurovisceral Form 75
Niemann-Pick Disease Classical Infantile Form 75
Niemann-Pick Disease Neuronopathic Type 75
Classical Niemann-Pick Disease 75
Niemann-Pick Disease Type I 75
Niemann-Pick Disease a 75
Niemann-Pick Diseases 73
Npda 75
Npa 75

Characteristics:

Orphanet epidemiological data:

59
niemann-pick disease type a
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
death by age 3 years
more common in ashkenazi jews
allelic disorder to nieman-pick disease type b


HPO:

32
niemann-pick disease, type a:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases Eye diseases Immune diseases Respiratory diseases
See all MalaCards categories (disease lists)
ICD10: 33 34
Orphanet: 59  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


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Summaries for Niemann-Pick Disease, Type a

About this section
OMIM : 57 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). Knudson and Kaplan (1962) suggested that 3 types of the disorder can be distinguished: infantile cerebral, juvenile cerebral, and noncerebral. Later, 5 forms of Niemann-Pick disease were distinguished. Four were delineated by Crocker (1961): the classical infantile form (type A), the visceral form (type B), the subacute or juvenile form (type C; 257220), and the Nova Scotian variant (type D; see 257220). The fifth, the adult form (type E; see 607616), was described by Terry et al. (1954) and Lynn and Terry (1964). Schneider et al. (1978) used the designation type F (see 607616) for a form characterized in 2 patients by a thermolabile enzyme. Most patients fall into Crocker's group A, with death before age 3 years. Schuchman (2007) provided a detailed review of Niemann-Pick disease type A, including clinical management. (257200)

MalaCards based summary : Niemann-Pick Disease, Type a, also known as sphingomyelinase deficiency, is related to niemann-pick disease and niemann-pick disease, type b, and has symptoms including constipation, vomiting and muscle weakness. An important gene associated with Niemann-Pick Disease, Type a is SMPD1 (Sphingomyelin Phosphodiesterase 1), and among its related pathways/superpathways are Neuroscience and Neural Crest Differentiation. The drugs Miglustat and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and brain, and related phenotypes are osteoporosis and xanthomatosis

Disease Ontology : 12 A Niemann-Pick disease characterized by onset in infancy and involvement of neurological tissues that has material basis in an autosomal recessive mutation of SMPD1 on chromosome 11p15.4.

NIH Rare Diseases : 53 Niemann-Pick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. In people with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain. Niemann-Pick disease type A appears during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to gain weight and grow at the expected rate (failure to thrive), and progressive deterioration of the nervous system. Due to the involvement of the nervous system, Niemann-Pick disease type A is also known as the neurological type. There is currently no effective treatment for this condition and those who are affected generally do not survive past early childhood. Niemann-Pick disease type A is caused by mutations in the SMPD1 gene. It is inherited in an autosomal recessive pattern. 

UniProtKB/Swiss-Prot : 75 Niemann-Pick disease A: An early-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. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, mental retardation, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. 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.

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Related Diseases for Niemann-Pick Disease, Type a

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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 a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 niemann-pick disease 32.4 CHIT1 SMPD1 UGT8
2 niemann-pick disease, type b 11.9
3 acid sphingomyelinase deficiency 11.7
4 gaucher's disease 10.1
5 thyroiditis 10.1
6 thyroid cancer 10.0
7 tremor 10.0
8 wallerian degeneration 9.9 MAG MPZ
9 myocardial infarction 9.8
10 acute myocardial infarction 9.8
11 status epilepticus 9.8
12 epilepsy 9.8
13 cocaine dependence 9.8
14 allergic encephalomyelitis 9.8 MBP PLP1
15 krabbe disease 9.8 CHIT1 MBP
16 isolated optic neuritis 9.7 CNP MBP
17 central pontine myelinolysis 9.7 MAG MBP
18 spindle cell synovial sarcoma 9.7 MAG MBP
19 sensory peripheral neuropathy 9.7 MAG MPZ
20 leukodystrophy, hypomyelinating, 2 9.7 MBP PLP1
21 primary progressive multiple sclerosis 9.6 MBP PLP1
22 congenital hypomyelination neuropathy 9.6 MBP MPZ
23 guillain-barre syndrome 9.3 MBP MPZ
24 peripheral nervous system disease 9.3 MAG MPZ
25 demyelinating disease 9.3 MAG MBP PLP1
26 hyperphenylalaninemia 9.2 CNP MBP
27 mannosidosis, beta a, lysosomal 9.2 CNP MAG MBP
28 polyradiculoneuropathy 9.1 MAG MBP MPZ
29 neuritis 9.1 MAG MBP MPZ
30 oligodendroglioma 9.1 CNP MBP UGT8
31 polyneuropathy 9.0 MAG MBP MPZ
32 hereditary neuropathies 8.6 MAG MBP MPZ PLP1
33 optic neuritis 8.6 MAG MBP MPZ PLP1
34 pelizaeus-merzbacher disease 8.6 MAG MBP MPZ PLP1
35 charcot-marie-tooth disease 8.5 MAG MBP MPZ PLP1
36 multiple sclerosis 7.6 CHIT1 CNP MAG MBP MPZ PLP1

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



Diseases related to Niemann-Pick Disease, Type a
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Symptoms & Phenotypes for Niemann-Pick Disease, Type a

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Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
muscle weakness
hyporeflexia
hypotonia
mental retardation
psychomotor retardation
more
Abdomen Gastrointestinal:
constipation
vomiting
feeding difficulties

Abdomen Liver:
hepatomegaly
neonatal jaundice

Skeletal:
osteoporosis

Immunology:
lymphadenopathy

Abdomen External Features:
protuberant abdomen

Growth Weight:
low body weight

Skin Nails Hair Skin:
xanthomas

Growth Other:
failure to thrive

AbdomenSpleen:
splenomegaly

Growth Height:
short stature

Hematology:
microcytic anemia
large vacuolated foam cells ('np cells') on bone marrow biopsy
'sea blue' histiocytes

Respiratory Lung:
diffuse reticular or finely nodular infiltrations

Respiratory:
frequent respiratory infections

Head And Neck Eyes:
cherry-red maculae (50%)
gray, granular-appearing maculae

Laboratory Abnormalities:
decreased acid sphingomyelinase activity (less than 5%)
multiple organs (lung, liver, spleen, kidney, brain) contain foamy resident cells and histiocytes
electron microscopy of foam cells shows lamellar inclusions


Clinical features from OMIM:

257200

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

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 osteoporosis 32 HP:0000939
2 xanthomatosis 32 HP:0000991
3 intellectual disability 32 HP:0001249
4 muscular hypotonia 32 HP:0001252
5 spasticity 32 HP:0001257
6 global developmental delay 32 HP:0001263
7 hyporeflexia 32 HP:0001265
8 generalized hypotonia 32 HP:0001290
9 muscle weakness 32 HP:0001324
10 failure to thrive 32 HP:0001508
11 protuberant abdomen 32 HP:0001538
12 splenomegaly 32 HP:0001744
13 microcytic anemia 32 HP:0001935
14 sea-blue histiocytosis 32 HP:0001982
15 vomiting 32 HP:0002013
16 constipation 32 HP:0002019
17 rigidity 32 HP:0002063
18 recurrent respiratory infections 32 HP:0002205
19 diffuse reticular or finely nodular infiltrations 32 HP:0002207
20 hepatomegaly 32 HP:0002240
21 athetosis 32 HP:0002305
22 lymphadenopathy 32 HP:0002716
23 foam cells with lamellar inclusion bodies 32 HP:0003609
24 short stature 32 HP:0004322
25 bone-marrow foam cells 32 HP:0004333
26 prolonged neonatal jaundice 32 HP:0006579
27 feeding difficulties in infancy 32 HP:0008872
28 cherry red spot of the macula 32 frequent (33%) HP:0010729

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


constipation, vomiting, muscle weakness

MGI Mouse Phenotypes related to Niemann-Pick Disease, Type a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.91 CNP MAG MBP MPZ PLP1 SMPD1
2 hematopoietic system MP:0005397 9.8 CNP MAG MBP MPZ PLP1 SMPD1
3 homeostasis/metabolism MP:0005376 9.8 CNP MAG MBP MPZ PLP1 SMPD1
4 immune system MP:0005387 9.76 CHIT1 CNP MAG MBP MPZ PLP1
5 nervous system MP:0003631 9.5 CNP MAG MBP MPZ PLP1 SMPD1
6 reproductive system MP:0005389 9.02 MBP MPZ PLP1 SMPD1 CNP
Sources

Drugs & Therapeutics for Niemann-Pick Disease, Type a

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

(show all 43)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miglustat Approved Phase 3,Phase 2,Phase 1 72599-27-0 51634
2
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
3
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
4
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
5
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
6
1-Deoxynojirimycin Experimental Phase 3,Phase 2 19130-96-2 1374
7 Prednisolone acetate Phase 2, Phase 3
8 Alkylating Agents Phase 2, Phase 3
9 Methylprednisolone acetate Phase 2, Phase 3
10 Methylprednisolone Hemisuccinate Phase 2, Phase 3
11 Glycoside Hydrolase Inhibitors Phase 3,Phase 2,Phase 1
12 Hypoglycemic Agents Phase 3,Phase 2,Phase 1
13 Immunosuppressive Agents Phase 2, Phase 3
14 Prednisolone hemisuccinate Phase 2, Phase 3
15 Prednisolone phosphate Phase 2, Phase 3
16 Anti-Infective Agents Phase 3,Phase 2,Phase 1
17 Anti-HIV Agents Phase 3,Phase 2,Phase 1
18 Anti-Retroviral Agents Phase 3,Phase 2,Phase 1
19 Antilymphocyte Serum Phase 2, Phase 3
20 Antirheumatic Agents Phase 2, Phase 3
21 Antiviral Agents Phase 3,Phase 2,Phase 1
22 Cardiac Glycosides Phase 3,Phase 2,Phase 1
23 Antineoplastic Agents, Alkylating Phase 2, Phase 3
24 Pharmaceutical Solutions Phase 2, Phase 3,Phase 1
25 Liver Extracts Phase 2, Phase 3,Phase 3
26
Acetylcysteine Approved, Investigational Phase 1, Phase 2 616-91-1 12035
27
Vorinostat Approved, Investigational Phase 1, Phase 2 149647-78-9 5311
28
alemtuzumab Approved, Investigational Phase 2 216503-57-0
29
Betadex Experimental Phase 1, Phase 2 7585-39-9 320761
30 Respiratory System Agents Phase 1, Phase 2
31 Histone Deacetylase Inhibitors Phase 1, Phase 2
32 N-monoacetylcystine Phase 1, Phase 2
33 Expectorants Phase 1, Phase 2
34 Antidotes Phase 1, Phase 2
35 Antioxidants Phase 1, Phase 2
36 Protective Agents Phase 1, Phase 2
37 Lithium carbonate Phase 1, Phase 2 554-13-2
38 Central Nervous System Depressants Phase 1, Phase 2
39 Tranquilizing Agents Phase 1, Phase 2
40 Antidepressive Agents Phase 1, Phase 2
41 Psychotropic Drugs Phase 1, Phase 2
42 Antimanic Agents Phase 1, Phase 2
43 cysteine Nutraceutical Phase 1, Phase 2

Interventional clinical trials:

(show all 38)
# Name Status NCT ID Phase Drugs
1 Application of Miglustat in Patients With Niemann-Pick Type C Completed NCT01760564 Phase 3 Miglustat
2 Stem Cell Transplant for Inborn Errors of Metabolism Completed NCT00176904 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Antithymocyte Globulin
3 Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency Recruiting NCT02004691 Phase 2, Phase 3 placebo (saline);GZ402665
4 Arimoclomol Prospective Study in Patients Diagnosed With NiemannPick Disease Type C Active, not recruiting NCT02612129 Phase 2, Phase 3 arimoclomol;Placebo
5 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
6 SurVival of Lysosomal Acid Lipase Deficiency (LAL-D) Infants Treated With SebelipAse aLfa Active, not recruiting NCT01371825 Phase 2, Phase 3 Sebelipase alfa (SBC-102)
7 ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases Terminated NCT00654433 Phase 3
8 Children With Lysosomal Acid Lipase Deficiency Who Previously Received Treatment With SBC-102 Terminated NCT01473875 Phase 2, Phase 3 SBC-102
9 Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 Completed NCT02124083 Phase 1, Phase 2 Vorinostat
10 Miglustat in Niemann-Pick Type C Disease Completed NCT00517153 Phase 2 miglustat
11 Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine Completed NCT00975689 Phase 1, Phase 2 N-Acetyl Cysteine
12 Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells Completed NCT00730314 Phase 1, Phase 2
13 Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C Recruiting NCT03471143 Phase 1, Phase 2 2-Hydroxypropyl-Beta-Cyclodextrin
14 Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency Recruiting NCT02292654 Phase 1, Phase 2 Olipudase alfa
15 Study of Pharmacokinetics and Preliminary Efficacy in Patients With Niemann-Pick C1 Recruiting NCT02912793 Phase 1, Phase 2 Hydroxypropyl-beta-cyclodextrin
16 Study of Lithium Carbonate to Treat Niemann-Pick Type C1 Disease Recruiting NCT03201627 Phase 1, Phase 2 Lithium Carbonate
17 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
18 Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Active, not recruiting NCT02193867 Phase 2 sebelipase alfa
19 A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency Enrolling by invitation NCT02004704 Phase 2 GZ402665
20 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
21 Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients Completed NCT01722526 Phase 1 Recombinant human acid sphingomyelinase
22 Saccadic Eye Movements in Patients With Niemann-Pick Type C Disease Completed NCT00316498 Phase 1 OGT918
23 Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease Completed NCT01747135 Phase 1 VTS-270
24 Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1) Recruiting NCT02939547 Phase 1 Hydroxypropyl-beta-cyclodextrin
25 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
26 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
27 Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease) Terminated NCT00410566 Phase 1 rhASM;rhASM;rhASM;rhASM;rhASM
28 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
29 Longitudinal Study of Cognition With Niemann-Pick Disease, Type C Completed NCT01899950
30 A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C Completed NCT02435030
31 PET Scan of Brain Metabolism in Relation to Age and Disease Completed NCT00001972 15 O Water
32 Evaluation of Biochemical Markers and Clinical Investigation of Niemann-Pick Disease, Type C Recruiting NCT00344331
33 Investigating Lysosomal Storage Diseases in Minority Groups Recruiting NCT02120235
34 Molecular and Cellular Mechanisms of Lysosomal Storage Diseases Recruiting NCT02000310
35 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
36 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
37 Biomarker for Niemann Pick Type C Disease Terminated NCT01306604
38 Screening of Niemann-Pick Disease, Type C in a Psychiatric Population Terminated NCT02841358 Not Applicable

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

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

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Genetic Tests for Niemann-Pick Disease, Type a

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

# Genetic test Affiliating Genes
1 Niemann-Pick Disease, Type a 29 SMPD1
2 Niemann-Pick Disease, Intermediate, Protracted Neurovisceral 29
Sources

Anatomical Context for Niemann-Pick Disease, Type a

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

41
Liver, Bone, Brain, Bone Marrow, Lung, Spleen, Eye
Sources

Publications for Niemann-Pick Disease, Type a

About this section

Articles related to Niemann-Pick Disease, Type a:

(show all 29)
# Title Authors Year
1
Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A. ( 27484861 )
2016
2
Seven novel mutations of the SMPD1 gene in four Chinese patients with Niemann-Pick disease type A and prenatal diagnosis for four fetuses. ( 26851525 )
2016
3
Case Report: Genetic analysis and anesthetic management of a child with Niemann-Pick disease Type A. ( 26913189 )
2015
4
Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B. ( 23252888 )
2013
5
New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report. ( 23724191 )
2013
6
Neonatal chitotriosidase activity is not predictive for Niemann-Pick disease type A/B: implications for newborn screening for lysosomal storage disorders. ( 23228552 )
2013
7
Merits of combination cortical, subcortical, and cerebellar injections for the treatment of Niemann-Pick disease type A. ( 22828503 )
2012
8
Niemann-Pick disease type A presenting as unilateral tremors. ( 23255701 )
2012
9
Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice. ( 21214563 )
2011
10
Alterations of myelin-specific proteins and sphingolipids characterize the brains of acid sphingomyelinase-deficient mice, an animal model of Niemann-Pick disease type A. ( 19187445 )
2009
11
Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A. ( 19642505 )
2009
12
Quantitative evaluation of sphingomyelin and glucosylceramide using matrix-assisted laser desorption ionization time-of-flight mass spectrometry with sphingosylphosphorylcholine as an internal standard. Practical application to tissues from patients with Niemann-Pick disease types A and C, and Gaucher disease. ( 18502707 )
2008
13
Unsuccessful treatment attempt: cord blood stem cell transplantation in a patient with Niemann-Pick disease type A. ( 17960492 )
2007
14
Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C. ( 16972172 )
2006
15
Niemann-Pick disease type A and B are clinically but also enzymatically heterogeneous: pitfall in the laboratory diagnosis of sphingomyelinase deficiency associated with the mutation Q292 K. ( 14681755 )
2003
16
[Niemann-Pick disease [type A and B] (acid sphingomyelinase deficiencies)]. ( 9645083 )
1998
17
Niemann Pick Disease type A in Israeli Arabs: 677delT, a common novel single mutation. Mutations in brief no. 161. Online. ( 10694919 )
1998
18
Temporal bone histopathology of Niemann-Pick disease type A. ( 9282255 )
1997
19
Pathology of visceral organs and bone marrow in an acid sphingomyelinase deficient knock-out mouse line, mimicking human Niemann-Pick disease type A. A light and electron microscopic study. ( 9505258 )
1997
20
Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B. ( 8664904 )
1996
21
Sphingosylphosphocholine, a signaling molecule which accumulates in Niemann-Pick disease type A, stimulates DNA-binding activity of the transcription activator protein AP-1. ( 7597047 )
1995
22
Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A. ( 1718266 )
1991
23
Evidence for both endogenous and exogenous sources of the sphingomyelin storage in lymphoid cell lines from patients with Niemann-Pick disease types A and B. ( 3139926 )
1988
24
Placental ultrasonographic biochemical and histochemical studies in human fetuses affected with Niemann-Pick disease type A. ( 3887360 )
1985
25
Molecular forms of sphingomyelinase and non-specific phosphodiesterases in Epstein-Barr virus-transformed lymphoid cell lines from Niemann-Pick disease types A and B. ( 2986976 )
1985
26
Biochemical and ultrastructural findings in a lymphoid cell line from Niemann-Pick disease type A. ( 3006848 )
1985
27
Immunological studies on lysosomal sphingomyelinase: identification of a 28 000-Da component deficient in urine from patients with Niemann-Pick disease types A and B. ( 6099155 )
1984
28
Metabolism of sphingomyelin by intact cultured fibroblasts: differentiation of Niemann-Pick disease type A and B. ( 7092849 )
1982
29
In situ degradation of sphingomyelin by cultured normal fibroblasts and fibroblasts from patients with Niemann-Pick disease type A and C. ( 7181884 )
1982
Sources

Variations for Niemann-Pick Disease, Type a

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

75 (show all 46)
# Symbol AA change Variation ID SNP ID
1 SMPD1 p.Leu302Pro VAR_005060
2 SMPD1 p.Met382Ile VAR_005061
3 SMPD1 p.Asn389Thr VAR_005063
4 SMPD1 p.Arg496Leu VAR_005066
5 SMPD1 p.Gly577Ser VAR_005067
6 SMPD1 p.Tyr446Cys VAR_011388
7 SMPD1 p.Ser248Arg VAR_015287
8 SMPD1 p.His319Tyr VAR_015288
9 SMPD1 p.Phe463Ser VAR_015291
10 SMPD1 p.Pro475Leu VAR_015292
11 SMPD1 p.Tyr537His VAR_015293
12 SMPD1 p.Leu103Pro VAR_060872
13 SMPD1 p.Pro184Leu VAR_060877
14 SMPD1 p.Arg228Cys VAR_060882
15 SMPD1 p.Arg228His VAR_060883
16 SMPD1 p.Ala241Val VAR_060885
17 SMPD1 p.Gly245Ser VAR_060887
18 SMPD1 p.Glu246Lys VAR_060888
19 SMPD1 p.Asp251Glu VAR_060889
20 SMPD1 p.Asp278Ala VAR_060890
21 SMPD1 p.Gln292Lys VAR_060893
22 SMPD1 p.Tyr313His VAR_060895
23 SMPD1 p.Leu341Pro VAR_060898
24 SMPD1 p.Tyr367Cys VAR_060900
25 SMPD1 p.His421Arg VAR_060906
26 SMPD1 p.Leu450Pro VAR_060910
27 SMPD1 p.Tyr467Ser VAR_060913
28 SMPD1 p.Ala482Glu VAR_060916
29 SMPD1 p.Arg496His VAR_060922
30 SMPD1 p.Tyr517Cys VAR_060926
31 SMPD1 p.Trp533Arg VAR_060927
32 SMPD1 p.Arg600His VAR_060932
33 SMPD1 p.Trp209Arg VAR_068435
34 SMPD1 p.Asp251His VAR_068436
35 SMPD1 p.Cys226Arg VAR_075324
36 SMPD1 p.Gly245Asp VAR_075325
37 SMPD1 p.Cys385Arg VAR_075327
38 SMPD1 p.Phe570Leu VAR_075331
39 SMPD1 p.Leu214Arg VAR_077311
40 SMPD1 p.Pro253Ser VAR_077312
41 SMPD1 p.Gly317Arg VAR_077314
42 SMPD1 p.Leu341Arg VAR_077317
43 SMPD1 p.Asn389His VAR_077319
44 SMPD1 p.Trp391Arg VAR_077320
45 SMPD1 p.Gly424Ser VAR_077321
46 SMPD1 p.Asn492Ile VAR_077322

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

6
(show top 50) (show all 151)
# 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.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs120074117 GRCh38 Chromosome 11, 6394204: 6394204
3 SMPD1 NM_000543.4(SMPD1): c.1735G> A (p.Gly579Ser) single nucleotide variant Pathogenic rs120074119 GRCh37 Chromosome 11, 6415676: 6415676
4 SMPD1 NM_000543.4(SMPD1): c.1735G> A (p.Gly579Ser) single nucleotide variant Pathogenic rs120074119 GRCh38 Chromosome 11, 6394446: 6394446
5 SMPD1 NM_000543.4(SMPD1): c.788T> A (p.Leu263Ter) single nucleotide variant Pathogenic rs120074120 GRCh37 Chromosome 11, 6413083: 6413083
6 SMPD1 NM_000543.4(SMPD1): c.788T> A (p.Leu263Ter) single nucleotide variant Pathogenic rs120074120 GRCh38 Chromosome 11, 6391853: 6391853
7 SMPD1 SMPD1, 2-BP DEL, LEU178FS deletion Pathogenic
8 SMPD1 NM_000543.4(SMPD1): c.1152G> A (p.Met384Ile) single nucleotide variant Pathogenic rs120074121 GRCh37 Chromosome 11, 6414506: 6414506
9 SMPD1 NM_000543.4(SMPD1): c.1152G> A (p.Met384Ile) single nucleotide variant Pathogenic rs120074121 GRCh38 Chromosome 11, 6393276: 6393276
10 SMPD1 NM_000543.4(SMPD1): c.911T> C (p.Leu304Pro) single nucleotide variant Pathogenic rs120074124 GRCh37 Chromosome 11, 6413206: 6413206
11 SMPD1 NM_000543.4(SMPD1): c.911T> C (p.Leu304Pro) single nucleotide variant Pathogenic rs120074124 GRCh38 Chromosome 11, 6391976: 6391976
12 SMPD1 NM_000543.4(SMPD1): c.996delC (p.Phe333Serfs) deletion Pathogenic rs387906289 GRCh37 Chromosome 11, 6413291: 6413291
13 SMPD1 NM_000543.4(SMPD1): c.996delC (p.Phe333Serfs) deletion Pathogenic rs387906289 GRCh38 Chromosome 11, 6392061: 6392061
14 SMPD1 NM_000543.4(SMPD1): c.1177T> G (p.Trp393Gly) single nucleotide variant Pathogenic rs120074125 GRCh37 Chromosome 11, 6414531: 6414531
15 SMPD1 NM_000543.4(SMPD1): c.1177T> G (p.Trp393Gly) single nucleotide variant Pathogenic rs120074125 GRCh38 Chromosome 11, 6393301: 6393301
16 SMPD1 NM_000543.4(SMPD1): c.1267C> T (p.His423Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs120074126 GRCh37 Chromosome 11, 6414850: 6414850
17 SMPD1 NM_000543.4(SMPD1): c.1267C> T (p.His423Tyr) single nucleotide variant Pathogenic/Likely pathogenic rs120074126 GRCh38 Chromosome 11, 6393620: 6393620
18 SMPD1 NM_000543.4(SMPD1): c.1327C> T (p.Arg443Ter) single nucleotide variant Pathogenic rs120074127 GRCh37 Chromosome 11, 6414910: 6414910
19 SMPD1 NM_000543.4(SMPD1): c.1327C> T (p.Arg443Ter) single nucleotide variant Pathogenic rs120074127 GRCh38 Chromosome 11, 6393680: 6393680
20 SMPD1 NM_000543.4(SMPD1): c.880C> A (p.Gln294Lys) single nucleotide variant Pathogenic rs120074128 GRCh37 Chromosome 11, 6413175: 6413175
21 SMPD1 NM_000543.4(SMPD1): c.880C> A (p.Gln294Lys) single nucleotide variant Pathogenic rs120074128 GRCh38 Chromosome 11, 6391945: 6391945
22 SMPD1 NM_000543.4(SMPD1): c.1451C> A (p.Ala484Glu) single nucleotide variant Pathogenic rs267607075 GRCh37 Chromosome 11, 6415236: 6415236
23 SMPD1 NM_000543.4(SMPD1): c.1451C> A (p.Ala484Glu) single nucleotide variant Pathogenic rs267607075 GRCh38 Chromosome 11, 6394006: 6394006
24 SMPD1 NM_000543.4(SMPD1): c.1406A> C (p.Tyr469Ser) single nucleotide variant Pathogenic rs267607074 GRCh37 Chromosome 11, 6415191: 6415191
25 SMPD1 NM_000543.4(SMPD1): c.1406A> C (p.Tyr469Ser) single nucleotide variant Pathogenic rs267607074 GRCh38 Chromosome 11, 6393961: 6393961
26 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh37 Chromosome 11, 6414445: 6414445
27 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh38 Chromosome 11, 6393215: 6393215
28 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh37 Chromosome 11, 6415211: 6415211
29 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh38 Chromosome 11, 6393981: 6393981
30 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic/Likely pathogenic rs398123479 GRCh37 Chromosome 11, 6413052: 6413052
31 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic/Likely pathogenic rs398123479 GRCh38 Chromosome 11, 6391822: 6391822
32 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh37 Chromosome 11, 6413137: 6413144
33 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh38 Chromosome 11, 6391907: 6391914
34 SMPD1 NM_000543.4(SMPD1): c.739G> A (p.Gly247Ser) single nucleotide variant Pathogenic/Likely pathogenic rs587779408 GRCh37 Chromosome 11, 6413034: 6413034
35 SMPD1 NM_000543.4(SMPD1): c.739G> A (p.Gly247Ser) single nucleotide variant Pathogenic/Likely pathogenic rs587779408 GRCh38 Chromosome 11, 6391804: 6391804
36 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic rs727504166 GRCh37 Chromosome 11, 6412770: 6412770
37 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic rs727504166 GRCh38 Chromosome 11, 6391540: 6391540
38 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh37 Chromosome 11, 6412649: 6412649
39 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh38 Chromosome 11, 6391419: 6391419
40 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh37 Chromosome 11, 6412868: 6412868
41 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh38 Chromosome 11, 6391638: 6391638
42 SMPD1 NM_000543.4(SMPD1): c.96G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs786204506 GRCh38 Chromosome 11, 6390694: 6390694
43 SMPD1 NM_000543.4(SMPD1): c.96G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs786204506 GRCh37 Chromosome 11, 6411924: 6411924
44 SMPD1 NM_000543.4(SMPD1): c.518dupT (p.Ser174Leufs) duplication Likely pathogenic rs786204733 GRCh38 Chromosome 11, 6391583: 6391583
45 SMPD1 NM_000543.4(SMPD1): c.518dupT (p.Ser174Leufs) duplication Likely pathogenic rs786204733 GRCh37 Chromosome 11, 6412813: 6412813
46 SMPD1 NM_000543.4(SMPD1): c.538_539delTT (p.Leu180Alafs) deletion Pathogenic/Likely pathogenic rs786204694 GRCh38 Chromosome 11, 6391603: 6391604
47 SMPD1 NM_000543.4(SMPD1): c.538_539delTT (p.Leu180Alafs) deletion Pathogenic/Likely pathogenic rs786204694 GRCh37 Chromosome 11, 6412833: 6412834
48 SMPD1 NM_000543.4(SMPD1): c.1111_1112delCT (p.Leu371Phefs) deletion Likely pathogenic rs786204514 GRCh38 Chromosome 11, 6393235: 6393236
49 SMPD1 NM_000543.4(SMPD1): c.1111_1112delCT (p.Leu371Phefs) deletion Likely pathogenic rs786204514 GRCh37 Chromosome 11, 6414465: 6414466
50 SMPD1 NM_000543.4(SMPD1): c.1430C> T (p.Pro477Leu) single nucleotide variant Likely pathogenic rs753508874 GRCh38 Chromosome 11, 6393985: 6393985
Sources

Expression for Niemann-Pick Disease, Type a

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

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Pathways related to Niemann-Pick Disease, Type a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Neuroscience 4
11.87 CNP MAG MBP
2
Neural Crest Differentiation 1
11.27 MBP MPZ
3
MECP2 and Associated Rett Syndrome 1
10.92 CNP MAG MBP
4
Glial Cell Differentiation 1
9.83 CNP MAG MBP PLP1
Sources

GO Terms for Niemann-Pick Disease, Type a

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Cellular components related to Niemann-Pick Disease, Type a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.8 CNP MAG MBP MPZ PLP1 SMPD1
2 lysosome GO:0005764 9.5 CHIT1 MPZ SMPD1
3 myelin sheath adaxonal region GO:0035749 9.16 CNP MAG
4 myelin sheath GO:0043209 9.02 CNP MAG MBP MPZ PLP1
5 compact myelin GO:0043218 8.96 MAG MBP

Biological processes related to Niemann-Pick Disease, Type a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.61 CHIT1 SMPD1 UGT8
2 response to toxic substance GO:0009636 9.46 CNP MBP
3 chemical synaptic transmission GO:0007268 9.46 CNP MBP MPZ PLP1
4 glycosphingolipid metabolic process GO:0006687 9.4 SMPD1 UGT8
5 cell-cell adhesion via plasma-membrane adhesion molecules GO:0098742 9.37 MAG MPZ
6 central nervous system myelination GO:0022010 9.32 MAG PLP1
7 axon ensheathment GO:0008366 9.26 MBP PLP1
8 myelination GO:0042552 9.13 MBP MPZ PLP1
9 substantia nigra development GO:0021762 8.8 CNP MBP PLP1

Molecular functions related to Niemann-Pick Disease, Type a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity, acting on glycosyl bonds GO:0016798 8.96 CHIT1 SMPD1
2 structural constituent of myelin sheath GO:0019911 8.62 MBP PLP1
Sources

Sources for Niemann-Pick Disease, Type a

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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