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 58 30 13 6 45 41 74
Niemann-Pick Disease Type a 12 54 60 15
Sphingomyelinase Deficiency 58 54 76
Sphingomyelin Lipidosis 58 54 76
Niemann-Pick Disease, Intermediate, Protracted Neurovisceral 30 6
Niemann-Pick Disease Intermediate Protracted Neurovisceral 76
Niemann-Pick Disease Acute Neuronopathic Form 76
Niemann-Pick Disease Acute Neurovisceral Form 76
Niemann-Pick Disease Classical Infantile Form 76
Niemann-Pick Disease Neuronopathic Type 76
Classical Niemann-Pick Disease 76
Niemann-Pick Disease Type I 76
Niemann-Pick Disease a 76
Niemann-Pick Diseases 74
Npda 76
Npa 76

Characteristics:

Orphanet epidemiological data:

60
niemann-pick disease type a
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

58
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:

33
niemann-pick disease, type a:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Niemann-Pick Disease, Type a

OMIM : 58 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 1-Deoxynojirimycin have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and bone marrow, and related phenotypes are cherry red spot of the macula and intellectual disability

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 : 54 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 : 76 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 42)
# Related Disease Score Top Affiliating Genes
1 niemann-pick disease, type b 32.5 NPC1 NPC2 SMPD1
2 acid sphingomyelinase deficiency 32.3 NPC1 SMPD1
3 niemann-pick disease 31.4 CHIT1 NPC1 NPC2 SMPD1 UGT8
4 niemann-pick disease, type c1 31.2 NPC1 NPC2 SMPD1
5 thyroid cancer 10.3
6 gaucher's disease 10.3
7 tremor 10.1
8 tay-sachs disease 10.1
9 scapuloperoneal myopathy, x-linked dominant 10.1
10 immunoglobulin alpha deficiency 10.1
11 portal hypertension 10.1
12 gingival overgrowth 10.1
13 peripheral nervous system disease 10.1
14 neuropathy 10.1
15 myocardial infarction 10.1
16 acute myocardial infarction 10.1
17 status epilepticus 10.1
18 epilepsy 10.1
19 cocaine dependence 10.1
20 histiocytosis 10.0
21 atherosclerosis susceptibility 9.9
22 beckwith-wiedemann syndrome 9.9
23 fish-eye disease 9.9
24 thrombocytopenic purpura, autoimmune 9.9
25 sea-blue histiocyte disease 9.9
26 muscle hypertrophy 9.9
27 graft-versus-host disease 9.9
28 infantile liver failure syndrome 1 9.9
29 brain injury 9.9
30 lysosomal storage disease 9.9
31 systemic scleroderma 9.9
32 purpura 9.9
33 hyperglycemia 9.9
34 niemann-pick disease type c, severe perinatal form 9.8 NPC1 NPC2
35 niemann-pick disease type c, late infantile neurologic onset 9.8 NPC1 NPC2
36 niemann-pick disease type c, severe early infantile neurologic onset 9.8 NPC1 NPC2
37 niemann-pick disease type c, adult neurologic onset 9.8 NPC1 NPC2
38 niemann-pick disease type c, juvenile neurologic onset 9.8 NPC1 NPC2
39 niemann-pick disease, type c2 9.6 NPC1 NPC2 SMPD1
40 glycine n-methyltransferase deficiency 9.5 NPC1 NPC2
41 sphingolipidosis 9.5 NPC1 NPC2 SMPD1
42 lipid storage disease 9.4 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

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

33 (show all 29)
# Description HPO Frequency HPO Source Accession
1 cherry red spot of the macula 33 frequent (33%) HP:0010729
2 intellectual disability 33 HP:0001249
3 muscular hypotonia 33 HP:0001252
4 spasticity 33 HP:0001257
5 muscle weakness 33 HP:0001324
6 failure to thrive 33 HP:0001508
7 constipation 33 HP:0002019
8 global developmental delay 33 HP:0001263
9 splenomegaly 33 HP:0001744
10 recurrent respiratory infections 33 HP:0002205
11 hepatomegaly 33 HP:0002240
12 short stature 33 HP:0004322
13 feeding difficulties in infancy 33 HP:0008872
14 vomiting 33 HP:0002013
15 osteoporosis 33 HP:0000939
16 microcytic anemia 33 HP:0001935
17 rigidity 33 HP:0002063
18 hyporeflexia 33 HP:0001265
19 lymphadenopathy 33 HP:0002716
20 prolonged neonatal jaundice 33 HP:0006579
21 generalized hypotonia 33 HP:0001290
22 athetosis 33 HP:0002305
23 xanthomatosis 33 HP:0000991
24 diffuse reticular or finely nodular infiltrations 33 HP:0002207
25 sea-blue histiocytosis 33 HP:0001982
26 protuberant abdomen 33 HP:0001538
27 bone-marrow foam cells 33 HP:0004333
28 psychomotor retardation 33 HP:0025356
29 foam cells with lamellar inclusion bodies 33 HP:0003609

Symptoms via clinical synopsis from OMIM:

58
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

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


muscle weakness, constipation, vomiting

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00381-A-1 9.28 CHIT1 MPZ SMPD1 UGT8
2 Decreased viability GR00381-A-3 9.28 MPZ
3 Decreased viability GR00402-S-2 9.28 CHIT1 MPZ SMPD1 UGT8

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.55 MPZ NPC1 NPC2 SMPD1 UGT8
2 immune system MP:0005387 9.43 CHIT1 MPZ NPC1 NPC2 SMPD1 UGT8
3 nervous system MP:0003631 9.02 MPZ NPC1 NPC2 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 top 50) (show all 51)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miglustat Approved Phase 4,Phase 3,Phase 2,Phase 1 72599-27-0 51634
2
1-Deoxynojirimycin Investigational Phase 4,Phase 3,Phase 2 19130-96-2 1374
3 Cardiac Glycosides Phase 4,Phase 3,Phase 2,Phase 1
4 Anti-Infective Agents Phase 4,Phase 3,Phase 2,Phase 1
5 Antiviral Agents Phase 4,Phase 3,Phase 2,Phase 1
6 Anti-HIV Agents Phase 4,Phase 3,Phase 2,Phase 1
7 Anti-Retroviral Agents Phase 4,Phase 3,Phase 2,Phase 1
8 Hypoglycemic Agents Phase 4,Phase 3,Phase 2,Phase 1
9 Glycoside Hydrolase Inhibitors Phase 4,Phase 3,Phase 2,Phase 1
10
Prednisolone phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
11
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 6741
12
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
13
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5
14
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
15
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 5755
16
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7
17 Prednisolone acetate Phase 2, Phase 3
18 Antineoplastic Agents, Alkylating 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 Immunosuppressive Agents Phase 2, Phase 3
23 Antilymphocyte Serum Phase 2, Phase 3
24 Antirheumatic Agents 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
Emodepside Investigational, Vet_approved Phase 1, Phase 2 155030-63-0
34 Histone Deacetylase Inhibitors Phase 1, Phase 2
35 N-monoacetylcystine Phase 1, Phase 2
36 Free Radical Scavengers Phase 1, Phase 2
37 Antidotes Phase 1, Phase 2
38 Antioxidants Phase 1, Phase 2
39 Expectorants Phase 1, Phase 2
40 cysteine Phase 1, Phase 2
41 Respiratory System Agents Phase 1, Phase 2
42 Protective Agents Phase 1, Phase 2
43
Bilirubin Phase 1, Phase 2 635-65-4, 69853-43-6 21252250 5280352
44 Central Nervous System Depressants Phase 1, Phase 2
45 Antidepressive Agents Phase 1, Phase 2
46 Psychotropic Drugs Phase 1, Phase 2
47 Tranquilizing Agents Phase 1, Phase 2
48 Antimanic Agents Phase 1, Phase 2
49 leucine Phase 2
50 Antineoplastic Agents, Immunological Phase 2

Interventional clinical trials:

(show all 47)
# Name Status NCT ID Phase Drugs
1 Safety and Efficacy of Miglustat in Chinese NPC Patients Not yet recruiting NCT03910621 Phase 4 Miglustat
2 Application of Miglustat in Patients With Niemann-Pick Type C Completed NCT01760564 Phase 3 Miglustat
3 Stem Cell Transplant for Inborn Errors of Metabolism Completed NCT00176904 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Antithymocyte Globulin
4 Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency Completed NCT01371825 Phase 2, Phase 3 Sebelipase alfa (SBC-102)
5 Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD) Recruiting NCT03822013 Phase 3 Miglustat
6 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
7 Arimoclomol Prospective Study in Patients Diagnosed With NiemannPick Disease Type C Active, not recruiting NCT02612129 Phase 2, Phase 3 arimoclomol;Placebo
8 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
9 Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1 Not yet recruiting NCT03879655 Phase 2, Phase 3 VTS-270
10 ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases Terminated NCT00654433 Phase 3
11 Children With Lysosomal Acid Lipase Deficiency Who Previously Received Treatment With SBC-102 Terminated NCT01473875 Phase 2, Phase 3 SBC-102
12 Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 Completed NCT02124083 Phase 1, Phase 2 Vorinostat
13 Miglustat in Niemann-Pick Type C Disease Completed NCT00517153 Phase 2 miglustat
14 Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine Completed NCT00975689 Phase 1, Phase 2 N-Acetyl Cysteine
15 Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells Completed NCT00730314 Phase 1, Phase 2
16 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
17 Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1 Recruiting NCT03887533 Phase 1, Phase 2 VTS-270
18 Safety and Efficacy of Intravenous Trappsol Cyclo (HPBCD) in Niemann-Pick Type C Patients Recruiting NCT02912793 Phase 1, Phase 2 Hydroxypropyl-beta-cyclodextrin
19 Study of Lithium Carbonate to Treat Niemann-Pick Type C1 Disease Recruiting NCT03201627 Phase 1, Phase 2 Lithium Carbonate
20 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
21 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
22 Clinical Trial in Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency Active, not recruiting NCT02193867 Phase 2 sebelipase alfa
23 A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency Enrolling by invitation NCT02004704 Phase 2 GZ402665
24 N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC) Not yet recruiting NCT03759639 Phase 2 IB1001
25 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
26 Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
27 Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients Completed NCT01722526 Phase 1 Recombinant human acid sphingomyelinase
28 Saccadic Eye Movements in Patients With Niemann-Pick Type C Disease Completed NCT00316498 Phase 1 OGT918
29 Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease Completed NCT01747135 Phase 1 VTS-270
30 Open‐Label Study of Long‐Term Safety and Efficacy of Intravenous Trappsol Cyclo (HPβCD) in Niemann‐Pick Disease Type C Recruiting NCT03893071 Phase 1 Hydroxypropyl-β-cyclodextrin
31 Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1) Recruiting NCT02939547 Phase 1 Hydroxypropyl-beta-cyclodextrin
32 UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
33 Human Placental-Derived Stem Cell Transplantation Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
34 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
35 Investigating Lysosomal Storage Diseases in Minority Groups Unknown status NCT02120235
36 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
37 Longitudinal Study of Cognition With Niemann-Pick Disease, Type C Completed NCT01899950
38 A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C Completed NCT02435030
39 PET Scan of Brain Metabolism in Relation to Age and Disease Completed NCT00001972 15 O Water
40 Biomarker for Niemann Pick Type C Disease (BioNPC) Recruiting NCT01306604
41 Induced Pluripotent Stem Cells for Niemann Pick Disease Recruiting NCT03883750
42 Evaluation of Biochemical Markers and Clinical Investigation of Niemann-Pick Disease, Type C Recruiting NCT00344331
43 Molecular and Cellular Mechanisms of Lysosomal Storage Diseases Recruiting NCT02000310
44 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
45 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
46 An Open-label Treatment Protocol for VTS-270 in Patients With Neurologic Manifestations of NPC Available NCT03643562 VTS270
47 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 30 SMPD1
2 Niemann-Pick Disease, Intermediate, Protracted Neurovisceral 30

Anatomical Context for Niemann-Pick Disease, Type a

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

42
Brain, Bone, Bone Marrow, Spleen, Liver, Eye, Kidney

Publications for Niemann-Pick Disease, Type a

Articles related to Niemann-Pick Disease, Type a:

(show all 41)
# 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
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
Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A. ( 27484861 )
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
Neonatal chitotriosidase activity is not predictive for Niemann-Pick disease type A/B: implications for newborn screening for lysosomal storage disorders. ( 23228552 )
2013
8
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
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
ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. ( 19888064 )
2009
13
Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. ( 19405096 )
2009
14
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
15
Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A. ( 19642505 )
2009
16
Carrier screening in individuals of Ashkenazi Jewish descent. ( 18197057 )
2008
17
Unsuccessful treatment attempt: cord blood stem cell transplantation in a patient with Niemann-Pick disease type A. ( 17960492 )
2007
18
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
19
Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study. ( 15877209 )
2005
20
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
21
[Niemann-Pick disease [type A and B] (acid sphingomyelinase deficiencies)]. ( 9645083 )
1998
22
Niemann Pick Disease type A in Israeli Arabs: 677delT, a common novel single mutation. Mutations in brief no. 161. Online. ( 10694919 )
1998
23
Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency. ( 9266408 )
1997
24
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
25
Temporal bone histopathology of Niemann-Pick disease type A. ( 9282255 )
1997
26
Identification of three novel mutations in the acid sphinogomyelinase gene of Japanese patients with Niemann-Pick disease type A and B. ( 8664904 )
1996
27
Molecular analysis of the acid sphingomyelinase deficiency in a family with an intermediate form of Niemann-Pick disease. ( 7762557 )
1995
28
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
29
A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate. ( 8051942 )
1994
30
Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients. ( 1391960 )
1992
31
Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease. ( 1301192 )
1992
32
Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A. ( 1718266 )
1991
33
Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. ( 1885770 )
1991
34
Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients. ( 2023926 )
1991
35
Placental ultrasonographic biochemical and histochemical studies in human fetuses affected with Niemann-Pick disease type A. ( 3887360 )
1985
36
Biochemical and ultrastructural findings in a lymphoid cell line from Niemann-Pick disease type A. ( 3006848 )
1985
37
In situ degradation of sphingomyelin by cultured normal fibroblasts and fibroblasts from patients with Niemann-Pick disease type A and C. ( 7181884 )
1982
38
Metabolism of sphingomyelin by intact cultured fibroblasts: differentiation of Niemann-Pick disease type A and B. ( 7092849 )
1982
39
Chemical and biochemical studies in human fetuses affected with Niemann-Pick disease type A. ( 761400 )
1979
40
Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A. ( 345809 )
1977
41
Prenatal diagnosis of Niemann-Pick disease type A using chromogenic substrate. ( 69227 )
1977

Variations for Niemann-Pick Disease, Type a

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

76 (show all 46)
# Symbol AA change Variation ID SNP ID
1 SMPD1 p.Leu304Pro VAR_005060 rs120074124
2 SMPD1 p.Met384Ile VAR_005061 rs120074121
3 SMPD1 p.Asn391Thr VAR_005063
4 SMPD1 p.Arg498Leu VAR_005066 rs120074117
5 SMPD1 p.Gly579Ser VAR_005067 rs120074119
6 SMPD1 p.Tyr448Cys VAR_011388 rs747143343
7 SMPD1 p.Ser250Arg VAR_015287 rs750779804
8 SMPD1 p.His321Tyr VAR_015288
9 SMPD1 p.Phe465Ser VAR_015291 rs131964322
10 SMPD1 p.Pro477Leu VAR_015292 rs753508874
11 SMPD1 p.Tyr539His VAR_015293
12 SMPD1 p.Leu105Pro VAR_060872 rs751269562
13 SMPD1 p.Pro186Leu VAR_060877 rs105751719
14 SMPD1 p.Arg230Cys VAR_060882 rs989639224
15 SMPD1 p.Arg230His VAR_060883 rs141387770
16 SMPD1 p.Ala243Val VAR_060885 rs129195801
17 SMPD1 p.Gly247Ser VAR_060887 rs587779408
18 SMPD1 p.Glu248Lys VAR_060888 rs200763423
19 SMPD1 p.Asp253Glu VAR_060889
20 SMPD1 p.Asp280Ala VAR_060890
21 SMPD1 p.Gln294Lys VAR_060893 rs120074128
22 SMPD1 p.Tyr315His VAR_060895
23 SMPD1 p.Leu343Pro VAR_060898
24 SMPD1 p.Tyr369Cys VAR_060900 rs372287825
25 SMPD1 p.His423Arg VAR_060906 rs767492080
26 SMPD1 p.Leu452Pro VAR_060910
27 SMPD1 p.Tyr469Ser VAR_060913 rs267607074
28 SMPD1 p.Ala484Glu VAR_060916 rs267607075
29 SMPD1 p.Arg498His VAR_060922 rs120074117
30 SMPD1 p.Tyr519Cys VAR_060926
31 SMPD1 p.Trp535Arg VAR_060927
32 SMPD1 p.Arg602His VAR_060932 rs370129081
33 SMPD1 p.Trp211Arg VAR_068435
34 SMPD1 p.Asp253His VAR_068436 rs398123479
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 rs757934797
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 279)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMPD1 NM_000543.4(SMPD1): c.714A> G (p.Ala238=) single nucleotide variant Benign/Likely benign rs2682091 GRCh37 Chromosome 11, 6413009: 6413009
2 SMPD1 NM_000543.4(SMPD1): c.1589G> C (p.Gly530Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs35122256 GRCh37 Chromosome 11, 6415530: 6415530
3 SMPD1 NM_000543.4(SMPD1): c.1675G> C (p.Val559Leu) single nucleotide variant Uncertain significance rs149939736 GRCh37 Chromosome 11, 6415616: 6415616
4 SMPD1 NM_000543.4(SMPD1): c.1675G> C (p.Val559Leu) single nucleotide variant Uncertain significance rs149939736 GRCh38 Chromosome 11, 6394386: 6394386
5 SMPD1 NM_000543.4(SMPD1): c.1783_1784delCT (p.Ala597Profs) deletion Likely pathogenic rs1437508852 GRCh37 Chromosome 11, 6415721: 6415723
6 SMPD1 NM_000543.4(SMPD1): c.1783_1784delCT (p.Ala597Profs) deletion Likely pathogenic rs1437508852 GRCh38 Chromosome 11, 6394494: 6394495
7 SMPD1 NM_000543.4(SMPD1): c.1280A> G (p.His427Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 6393633: 6393633
8 SMPD1 NM_000543.4(SMPD1): c.1280A> G (p.His427Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 6414863: 6414863
9 SMPD1 NM_000543.4(SMPD1): c.1055A> C (p.Glu352Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 6413350: 6413350
10 SMPD1 NM_000543.4(SMPD1): c.1055A> C (p.Glu352Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 6392120: 6392120
11 SMPD1 NM_000543.4(SMPD1): c.1379delC (p.Thr460Ilefs) deletion Likely pathogenic rs1554935285 GRCh37 Chromosome 11, 6415163: 6415164
12 SMPD1 NM_000543.4(SMPD1): c.958A> G (p.Asn320Asp) single nucleotide variant Uncertain significance rs779927660 GRCh38 Chromosome 11, 6392023: 6392023
13 SMPD1 NM_000543.4(SMPD1): c.958A> G (p.Asn320Asp) single nucleotide variant Uncertain significance rs779927660 GRCh37 Chromosome 11, 6413253: 6413253
14 SMPD1 NM_000543.4(SMPD1): c.898_900dup (p.Thr300_Val301insThr) duplication Uncertain significance rs1554934463 GRCh38 Chromosome 11, 6391963: 6391965
15 SMPD1 NM_000543.4(SMPD1): c.898_900dup (p.Thr300_Val301insThr) duplication Uncertain significance rs1554934463 GRCh37 Chromosome 11, 6413189: 6413189
16 SMPD1 NM_000543.4(SMPD1): c.894_902del9 (p.Thr300_Thr302del) deletion Uncertain significance rs1554934457 GRCh38 Chromosome 11, 6391959: 6391967
17 SMPD1 NM_000543.4(SMPD1): c.894_902del9 (p.Thr300_Thr302del) deletion Uncertain significance rs1554934457 GRCh37 Chromosome 11, 6413187: 6413196
18 SMPD1 NM_000543.4(SMPD1): c.778G> T (p.Glu260Ter) single nucleotide variant Likely pathogenic rs1554934406 GRCh38 Chromosome 11, 6391843: 6391843
19 SMPD1 NM_000543.4(SMPD1): c.778G> T (p.Glu260Ter) single nucleotide variant Likely pathogenic rs1554934406 GRCh37 Chromosome 11, 6413073: 6413073
20 SMPD1 NM_000543.4(SMPD1): c.1379delC (p.Thr460Ilefs) deletion Likely pathogenic rs1554935285 GRCh38 Chromosome 11, 6393934: 6393934
21 SMPD1 NM_000543.4(SMPD1): c.750C> A (p.Ser250Arg) single nucleotide variant Likely pathogenic rs1423504237 GRCh38 Chromosome 11, 6391815: 6391815
22 SMPD1 NM_000543.4(SMPD1): c.750C> A (p.Ser250Arg) single nucleotide variant Likely pathogenic rs1423504237 GRCh37 Chromosome 11, 6413045: 6413045
23 SMPD1 NM_000543.4(SMPD1): c.528delG (p.Trp176Terfs) deletion Likely pathogenic rs1554934210 GRCh38 Chromosome 11, 6391593: 6391593
24 SMPD1 NM_000543.4(SMPD1): c.130_147dup (p.Leu49_Ser50insAlaLeuAlaLeuAlaLeu) duplication Uncertain significance rs1554933850 GRCh38 Chromosome 11, 6390728: 6390745
25 SMPD1 NM_000543.4(SMPD1): c.130_147dup (p.Leu49_Ser50insAlaLeuAlaLeuAlaLeu) duplication Uncertain significance rs1554933850 GRCh37 Chromosome 11, 6411954: 6411954
26 SMPD1 NM_000543.4(SMPD1): c.95G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs1554933780 GRCh38 Chromosome 11, 6390693: 6390693
27 SMPD1 NM_000543.4(SMPD1): c.95G> A (p.Trp32Ter) single nucleotide variant Likely pathogenic rs1554933780 GRCh37 Chromosome 11, 6411923: 6411923
28 SMPD1 NM_000543.4(SMPD1): c.61C> T (p.Gln21Ter) single nucleotide variant Likely pathogenic rs1554933751 GRCh38 Chromosome 11, 6390659: 6390659
29 SMPD1 NM_000543.4(SMPD1): c.61C> T (p.Gln21Ter) single nucleotide variant Likely pathogenic rs1554933751 GRCh37 Chromosome 11, 6411889: 6411889
30 SMPD1 NM_000543.4(SMPD1): c.528delG (p.Trp176Terfs) deletion Likely pathogenic rs1554934210 GRCh37 Chromosome 11, 6412821: 6412822
31 SMPD1 NM_000543.4(SMPD1): c.28C> T (p.Gln10Ter) single nucleotide variant Likely pathogenic rs1205990349 GRCh38 Chromosome 11, 6390626: 6390626
32 SMPD1 NM_000543.4(SMPD1): c.28C> T (p.Gln10Ter) single nucleotide variant Likely pathogenic rs1205990349 GRCh37 Chromosome 11, 6411856: 6411856
33 SMPD1 NM_000543.4(SMPD1): c.1817delC (p.Pro606Leufs) deletion Likely pathogenic rs1554935746 GRCh38 Chromosome 11, 6394528: 6394528
34 SMPD1 NM_000543.4(SMPD1): c.1817delC (p.Pro606Leufs) deletion Likely pathogenic rs1554935746 GRCh37 Chromosome 11, 6415755: 6415756
35 SMPD1 NM_000543.4(SMPD1): c.1801G> A (p.Ala601Thr) single nucleotide variant Uncertain significance rs750433951 GRCh38 Chromosome 11, 6394512: 6394512
36 SMPD1 NM_000543.4(SMPD1): c.1801G> A (p.Ala601Thr) single nucleotide variant Uncertain significance rs750433951 GRCh37 Chromosome 11, 6415742: 6415742
37 SMPD1 NM_000543.4(SMPD1): c.1627G> T (p.Glu543Ter) single nucleotide variant Likely pathogenic rs756031857 GRCh38 Chromosome 11, 6394338: 6394338
38 SMPD1 NM_000543.4(SMPD1): c.1627G> T (p.Glu543Ter) single nucleotide variant Likely pathogenic rs756031857 GRCh37 Chromosome 11, 6415568: 6415568
39 SMPD1 NM_000543.4(SMPD1): c.1491C> G (p.Tyr497Ter) single nucleotide variant Likely pathogenic rs1554935439 GRCh38 Chromosome 11, 6394202: 6394202
40 SMPD1 NM_000543.4(SMPD1): c.1491C> G (p.Tyr497Ter) single nucleotide variant Likely pathogenic rs1554935439 GRCh37 Chromosome 11, 6415432: 6415432
41 SMPD1 NM_000543.4(SMPD1): c.1361C> T (p.Ala454Val) single nucleotide variant Uncertain significance rs1402734026 GRCh38 Chromosome 11, 6393916: 6393916
42 SMPD1 NM_000543.4(SMPD1): c.1361C> T (p.Ala454Val) single nucleotide variant Uncertain significance rs1402734026 GRCh37 Chromosome 11, 6415146: 6415146
43 SMPD1 NM_000543.4(SMPD1): c.955G> C (p.Gly319Arg) single nucleotide variant Uncertain significance rs757934797 GRCh38 Chromosome 11, 6392020: 6392020
44 SMPD1 NM_000543.4(SMPD1): c.955G> C (p.Gly319Arg) single nucleotide variant Uncertain significance rs757934797 GRCh37 Chromosome 11, 6413250: 6413250
45 SMPD1 NM_000543.4(SMPD1): c.533T> A (p.Ile178Asn) single nucleotide variant Uncertain significance rs749780769 GRCh38 Chromosome 11, 6391598: 6391598
46 SMPD1 NM_000543.4(SMPD1): c.533T> A (p.Ile178Asn) single nucleotide variant Uncertain significance rs749780769 GRCh37 Chromosome 11, 6412828: 6412828
47 SMPD1 NM_000543.4(SMPD1): c.318+2T> A single nucleotide variant Likely pathogenic rs1225462507 GRCh38 Chromosome 11, 6390918: 6390918
48 SMPD1 NM_000543.4(SMPD1): c.318+2T> A single nucleotide variant Likely pathogenic rs1225462507 GRCh37 Chromosome 11, 6412148: 6412148
49 SMPD1 NM_000543.4(SMPD1): c.314T> C (p.Leu105Pro) single nucleotide variant Likely pathogenic rs751269562 GRCh38 Chromosome 11, 6390912: 6390912
50 SMPD1 NM_000543.4(SMPD1): c.314T> C (p.Leu105Pro) single nucleotide variant Likely pathogenic rs751269562 GRCh37 Chromosome 11, 6412142: 6412142

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 lysosome GO:0005764 9.02 CHIT1 MPZ NPC1 NPC2 SMPD1
2 lysosomal lumen GO:0043202 8.96 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 NPC2 NPC1

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

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