NPDA
MCID: NMN013
MIFTS: 57

Niemann-Pick Disease, Type a (NPDA)

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

Aliases & Classifications for Niemann-Pick Disease, Type a

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

Name: Niemann-Pick Disease, Type a 57 29 13 6 44 40 73
Niemann-Pick Disease Type a 12 53 59 15
Sphingomyelinase Deficiency 57 53 75
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:



Summaries for Niemann-Pick Disease, Type a

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 niemann-pick disease type a, is related to niemann-pick disease, type b and acid sphingomyelinase deficiency, and has symptoms including muscle weakness, constipation and vomiting. An important gene associated with Niemann-Pick Disease, Type a is SMPD1 (Sphingomyelin Phosphodiesterase 1), and among its related pathways/superpathways are Metabolism and Statin Pathway. The drugs Miglustat and Methylprednisolone hemisuccinate have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and bone marrow, and related phenotypes are intellectual disability and muscular hypotonia

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.

Related Diseases for Niemann-Pick Disease, Type a

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 32)
# Related Disease Score Top Affiliating Genes
1 niemann-pick disease, type b 32.6 NPC1 NPC2 SMPD1
2 acid sphingomyelinase deficiency 32.4 NPC1 SMPD1
3 niemann-pick disease 31.9 CHIT1 NPC1 NPC2 SMPD1 UGT8
4 niemann-pick disease, type c1 31.4 NPC1 NPC2 SMPD1
5 gaucher's disease 10.3
6 thyroid cancer 10.2
7 endocardial fibroelastosis 10.1
8 gingival overgrowth 10.1
9 peripheral nervous system disease 10.1
10 neuropathy 10.1
11 myocardial infarction 10.0
12 acute myocardial infarction 10.0
13 status epilepticus 10.0
14 epilepsy 10.0
15 cocaine dependence 10.0
16 niemann-pick disease type c, severe perinatal form 9.9 NPC1 NPC2
17 niemann-pick disease type c, late infantile neurologic onset 9.9 NPC1 NPC2
18 atherosclerosis susceptibility 9.9
19 beckwith-wiedemann syndrome 9.9
20 sea-blue histiocyte disease 9.9
21 graft-versus-host disease 9.9
22 infantile liver failure syndrome 1 9.9
23 lysosomal storage disease 9.9
24 histiocytosis 9.9
25 hyperglycemia 9.9
26 niemann-pick disease type c, severe early infantile neurologic onset 9.9 NPC1 NPC2
27 niemann-pick disease type c, adult neurologic onset 9.9 NPC1 NPC2
28 niemann-pick disease type c, juvenile neurologic onset 9.8 NPC1 NPC2
29 niemann-pick disease, type c2 9.7 NPC1 NPC2 SMPD1
30 glycine n-methyltransferase deficiency 9.7 NPC1 NPC2
31 sphingolipidosis 9.7 NPC1 NPC2 SMPD1
32 lipid storage disease 9.6 NPC1 NPC2 SMPD1

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



Diseases related to Niemann-Pick Disease, Type a

Symptoms & Phenotypes for Niemann-Pick Disease, Type a

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

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

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


muscle weakness, constipation, vomiting

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 NPC1 NPC2 PLP1 SMPD1 UGT8
2 growth/size/body region MP:0005378 9.55 NPC1 NPC2 PLP1 SMPD1 UGT8
3 immune system MP:0005387 9.43 CHIT1 NPC1 NPC2 PLP1 SMPD1 UGT8
4 nervous system MP:0003631 9.02 NPC1 NPC2 PLP1 SMPD1 UGT8

Drugs & Therapeutics for Niemann-Pick Disease, Type a

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

(show all 47)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miglustat Approved Phase 3,Phase 2,Phase 1 72599-27-0 51634
2
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5
3
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 6055-19-2, 50-18-0 2907
4
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
5
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
6
Prednisolone phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
7
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
8
1-Deoxynojirimycin Experimental, Investigational Phase 3,Phase 2 19130-96-2 1374
9
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7
10 Cardiac Glycosides Phase 3,Phase 2,Phase 1
11 Hypoglycemic Agents Phase 3,Phase 2,Phase 1
12 Antiviral Agents Phase 3,Phase 2,Phase 1
13 Glycoside Hydrolase Inhibitors Phase 3,Phase 2,Phase 1
14 Anti-Retroviral Agents Phase 3,Phase 2,Phase 1
15 Anti-Infective Agents Phase 3,Phase 2,Phase 1
16 Anti-HIV Agents Phase 3,Phase 2,Phase 1
17 Prednisolone acetate Phase 2, Phase 3
18 Immunosuppressive Agents Phase 2, Phase 3
19 Methylprednisolone acetate Phase 2, Phase 3
20 Alkylating Agents Phase 2, Phase 3
21 Immunologic Factors Phase 2, Phase 3
22 Antineoplastic Agents, Alkylating Phase 2, Phase 3
23 Antirheumatic Agents Phase 2, Phase 3
24 Antilymphocyte Serum Phase 2, Phase 3
25 Liver Extracts Phase 2, Phase 3,Phase 3,Phase 1
26 Pharmaceutical Solutions Phase 2, Phase 3,Phase 1
27
Vorinostat Approved, Investigational Phase 1, Phase 2 149647-78-9 5311
28
Acetylcysteine Approved, Investigational Phase 1, Phase 2 616-91-1 12035
29
Lithium carbonate Approved Phase 1, Phase 2 554-13-2
30
alemtuzumab Approved, Investigational Phase 2 216503-57-0
31
Glycine Approved, Nutraceutical, Vet_approved Phase 1, Phase 2 56-40-6 750
32
Betadex Experimental Phase 1, Phase 2,Phase 2 7585-39-9 320761
33 Histone Deacetylase Inhibitors Phase 1, Phase 2
34 Expectorants Phase 1, Phase 2
35 Respiratory System Agents Phase 1, Phase 2
36 Antioxidants Phase 1, Phase 2
37 Free Radical Scavengers Phase 1, Phase 2
38 Antidotes Phase 1, Phase 2
39 Protective Agents Phase 1, Phase 2
40 N-monoacetylcystine Phase 1, Phase 2
41 cysteine Phase 1, Phase 2
42
Bilirubin Phase 1, Phase 2 635-65-4 5280352
43 Antidepressive Agents Phase 1, Phase 2
44 Psychotropic Drugs Phase 1, Phase 2
45 Antimanic Agents Phase 1, Phase 2
46 Tranquilizing Agents Phase 1, Phase 2
47 Central Nervous System Depressants Phase 1, Phase 2

Interventional clinical trials:

(show all 41)
# 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 Active, not 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 Study of Pharmacokinetics and Preliminary Efficacy in Patients With Niemann-Pick C1 Recruiting NCT02912793 Phase 1, Phase 2 Hydroxypropyl-beta-cyclodextrin
15 Study of Lithium Carbonate to Treat Niemann-Pick Type C1 Disease Recruiting NCT03201627 Phase 1, Phase 2 Lithium Carbonate
16 Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency Active, not recruiting NCT02292654 Phase 1, Phase 2 Olipudase alfa
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 N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC) Not yet recruiting NCT03759639 Phase 2 IB1001
21 Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease Not yet recruiting NCT03687476 Phase 2 VTS-270
22 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
23 Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients Completed NCT01722526 Phase 1 Recombinant human acid sphingomyelinase
24 Saccadic Eye Movements in Patients With Niemann-Pick Type C Disease Completed NCT00316498 Phase 1 OGT918
25 Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease Completed NCT01747135 Phase 1 VTS-270
26 Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1) Recruiting NCT02939547 Phase 1 Hydroxypropyl-beta-cyclodextrin
27 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
28 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
29 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
30 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
31 Longitudinal Study of Cognition With Niemann-Pick Disease, Type C Completed NCT01899950
32 A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C Completed NCT02435030
33 PET Scan of Brain Metabolism in Relation to Age and Disease Completed NCT00001972 15 O Water
34 Biomarker for Niemann Pick Type C Disease Recruiting NCT01306604
35 Evaluation of Biochemical Markers and Clinical Investigation of Niemann-Pick Disease, Type C Recruiting NCT00344331
36 Investigating Lysosomal Storage Diseases in Minority Groups Recruiting NCT02120235
37 Molecular and Cellular Mechanisms of Lysosomal Storage Diseases Recruiting NCT02000310
38 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
39 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
40 An Open-label Treatment Protocol for VTS-270 in Patients With Neurologic Manifestations of NPC Available NCT03643562 VTS270
41 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

Genetic Tests for Niemann-Pick Disease, Type a

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

Anatomical Context for Niemann-Pick Disease, Type a

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

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

Publications for Niemann-Pick Disease, Type a

Articles related to Niemann-Pick Disease, Type a:

(show all 29)
# Title Authors Year
1
Deep sequencing of SMPD1 gene revealed a heterozygous frameshift mutation (p.Ser192Alafs) in a Palestinian infant with Niemann-Pick disease type A: a case report. ( 30223864 )
2018
2
Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A. ( 27484861 )
2016
3
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
4
Case Report: Genetic analysis and anesthetic management of a child with Niemann-Pick disease Type A. ( 26913189 )
2015
5
Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a Niemann Pick disease type A mouse model. ( 24448491 )
2014
6
High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A. ( 24488099 )
2014
7
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
8
Neonatal chitotriosidase activity is not predictive for Niemann-Pick disease type A/B: implications for newborn screening for lysosomal storage disorders. ( 23228552 )
2013
9
Merits of combination cortical, subcortical, and cerebellar injections for the treatment of Niemann-Pick disease type A. ( 22828503 )
2012
10
Niemann-Pick disease type A presenting as unilateral tremors. ( 23255701 )
2012
11
Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice. ( 21214563 )
2011
12
Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A. ( 19642505 )
2009
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
Placental ultrasonographic biochemical and histochemical studies in human fetuses affected with Niemann-Pick disease type A. ( 3887360 )
1985
24
Biochemical and ultrastructural findings in a lymphoid cell line from Niemann-Pick disease type A. ( 3006848 )
1985
25
Metabolism of sphingomyelin by intact cultured fibroblasts: differentiation of Niemann-Pick disease type A and B. ( 7092849 )
1982
26
In situ degradation of sphingomyelin by cultured normal fibroblasts and fibroblasts from patients with Niemann-Pick disease type A and C. ( 7181884 )
1982
27
Chemical and biochemical studies in human fetuses affected with Niemann-Pick disease type A. ( 761400 )
1979
28
Prenatal diagnosis of Niemann-Pick disease type A using chromogenic substrate. ( 69227 )
1977
29
Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A. ( 345809 )
1977

Variations for Niemann-Pick Disease, Type a

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.Leu304Pro VAR_005060
2 SMPD1 p.Met384Ile VAR_005061
3 SMPD1 p.Asn391Thr VAR_005063
4 SMPD1 p.Arg498Leu VAR_005066
5 SMPD1 p.Gly579Ser VAR_005067
6 SMPD1 p.Tyr448Cys VAR_011388
7 SMPD1 p.Ser250Arg VAR_015287
8 SMPD1 p.His321Tyr VAR_015288
9 SMPD1 p.Phe465Ser VAR_015291
10 SMPD1 p.Pro477Leu VAR_015292
11 SMPD1 p.Tyr539His VAR_015293
12 SMPD1 p.Leu105Pro VAR_060872
13 SMPD1 p.Pro186Leu VAR_060877
14 SMPD1 p.Arg230Cys VAR_060882
15 SMPD1 p.Arg230His VAR_060883
16 SMPD1 p.Ala243Val VAR_060885
17 SMPD1 p.Gly247Ser VAR_060887
18 SMPD1 p.Glu248Lys VAR_060888
19 SMPD1 p.Asp253Glu VAR_060889
20 SMPD1 p.Asp280Ala VAR_060890
21 SMPD1 p.Gln294Lys VAR_060893
22 SMPD1 p.Tyr315His VAR_060895
23 SMPD1 p.Leu343Pro VAR_060898
24 SMPD1 p.Tyr369Cys VAR_060900
25 SMPD1 p.His423Arg VAR_060906
26 SMPD1 p.Leu452Pro VAR_060910
27 SMPD1 p.Tyr469Ser VAR_060913
28 SMPD1 p.Ala484Glu VAR_060916
29 SMPD1 p.Arg498His VAR_060922
30 SMPD1 p.Tyr519Cys VAR_060926
31 SMPD1 p.Trp535Arg VAR_060927
32 SMPD1 p.Arg602His VAR_060932
33 SMPD1 p.Trp211Arg VAR_068435
34 SMPD1 p.Asp253His VAR_068436
35 SMPD1 p.Cys228Arg VAR_075324
36 SMPD1 p.Gly247Asp VAR_075325
37 SMPD1 p.Cys387Arg VAR_075327
38 SMPD1 p.Phe572Leu VAR_075331
39 SMPD1 p.Leu216Arg VAR_077311
40 SMPD1 p.Pro255Ser VAR_077312
41 SMPD1 p.Gly319Arg VAR_077314
42 SMPD1 p.Leu343Arg VAR_077317
43 SMPD1 p.Asn391His VAR_077319
44 SMPD1 p.Trp393Arg VAR_077320
45 SMPD1 p.Gly426Ser VAR_077321
46 SMPD1 p.Asn494Ile VAR_077322

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

6 (show top 50) (show all 281)
# 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.1071C> T (p.Ala357=) single nucleotide variant Conflicting interpretations of pathogenicity rs72896268 GRCh37 Chromosome 11, 6413366: 6413366
27 SMPD1 NM_000543.4(SMPD1): c.1071C> T (p.Ala357=) single nucleotide variant Conflicting interpretations of pathogenicity rs72896268 GRCh38 Chromosome 11, 6392136: 6392136
28 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh37 Chromosome 11, 6414445: 6414445
29 SMPD1 NM_000543.4(SMPD1): c.1092-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs398123474 GRCh38 Chromosome 11, 6393215: 6393215
30 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh37 Chromosome 11, 6415211: 6415211
31 SMPD1 NM_000543.4(SMPD1): c.1426C> T (p.Arg476Trp) single nucleotide variant Pathogenic/Likely pathogenic rs182812968 GRCh38 Chromosome 11, 6393981: 6393981
32 SMPD1 NM_000543.4(SMPD1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs398123478 GRCh37 Chromosome 11, 6415565: 6415565
33 SMPD1 NM_000543.4(SMPD1): c.1624C> T (p.Arg542Ter) single nucleotide variant Pathogenic rs398123478 GRCh38 Chromosome 11, 6394335: 6394335
34 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic/Likely pathogenic rs398123479 GRCh37 Chromosome 11, 6413052: 6413052
35 SMPD1 NM_000543.4(SMPD1): c.757G> C (p.Asp253His) single nucleotide variant Pathogenic/Likely pathogenic rs398123479 GRCh38 Chromosome 11, 6391822: 6391822
36 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh37 Chromosome 11, 6413137: 6413144
37 SMPD1 NM_000543.4(SMPD1): c.842_849dupTCCCCGCA (p.His284Serfs) duplication Pathogenic rs281860677 GRCh38 Chromosome 11, 6391907: 6391914
38 SMPD1 NM_000543.4(SMPD1): c.739G> A (p.Gly247Ser) single nucleotide variant Pathogenic/Likely pathogenic rs587779408 GRCh37 Chromosome 11, 6413034: 6413034
39 SMPD1 NM_000543.4(SMPD1): c.739G> A (p.Gly247Ser) single nucleotide variant Pathogenic/Likely pathogenic rs587779408 GRCh38 Chromosome 11, 6391804: 6391804
40 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic/Likely pathogenic rs727504166 GRCh37 Chromosome 11, 6412770: 6412770
41 SMPD1 NM_000543.4(SMPD1): c.475T> C (p.Cys159Arg) single nucleotide variant Pathogenic/Likely pathogenic rs727504166 GRCh38 Chromosome 11, 6391540: 6391540
42 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh37 Chromosome 11, 6412649: 6412649
43 SMPD1 NM_000543.4(SMPD1): c.354delC (p.Ile119Serfs) deletion Pathogenic/Likely pathogenic rs727504165 GRCh38 Chromosome 11, 6391419: 6391419
44 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh37 Chromosome 11, 6412868: 6412868
45 SMPD1 NM_000543.4(SMPD1): c.573delT (p.Ser192Alafs) deletion Pathogenic rs727504167 GRCh38 Chromosome 11, 6391638: 6391638
46 SMPD1 NM_000543.4(SMPD1): c.96G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs786204506 GRCh38 Chromosome 11, 6390694: 6390694
47 SMPD1 NM_000543.4(SMPD1): c.96G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs786204506 GRCh37 Chromosome 11, 6411924: 6411924
48 SMPD1 NM_000543.4(SMPD1): c.518dupT (p.Ser174Leufs) duplication Likely pathogenic rs786204733 GRCh38 Chromosome 11, 6391583: 6391583
49 SMPD1 NM_000543.4(SMPD1): c.518dupT (p.Ser174Leufs) duplication Likely pathogenic rs786204733 GRCh37 Chromosome 11, 6412813: 6412813
50 SMPD1 NM_000543.4(SMPD1): c.538_539delTT (p.Leu180Alafs) deletion Pathogenic/Likely pathogenic rs786204694 GRCh38 Chromosome 11, 6391603: 6391604

Expression for Niemann-Pick Disease, Type a

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

Pathways for Niemann-Pick Disease, Type a

GO Terms for Niemann-Pick Disease, Type a

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

# Name GO ID Score Top Affiliating Genes
1 lysosomal lumen GO:0043202 8.96 NPC2 SMPD1
2 lysosome GO:0005764 8.92 CHIT1 NPC1 NPC2 SMPD1

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.54 NPC1 NPC2 UGT8
2 lipid transport GO:0006869 9.48 NPC1 NPC2
3 steroid metabolic process GO:0008202 9.46 NPC1 NPC2
4 cholesterol homeostasis GO:0042632 9.43 NPC1 NPC2
5 cholesterol metabolic process GO:0008203 9.4 NPC1 NPC2
6 glycosphingolipid metabolic process GO:0006687 9.32 SMPD1 UGT8
7 cholesterol transport GO:0030301 9.26 NPC1 NPC2
8 cholesterol efflux GO:0033344 9.16 NPC1 NPC2
9 low-density lipoprotein particle clearance GO:0034383 8.96 NPC1 NPC2
10 intracellular cholesterol transport GO:0032367 8.62 NPC1 NPC2

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 cholesterol binding GO:0015485 8.62 NPC1 NPC2

Sources for Niemann-Pick Disease, Type a

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
Content
Loading form....