Niemann-Pick disease type A

General Information (adopted from Orphanet):

Synonyms, Signs: SPHINGOMYELIN LIPIDOSIS
SPHINGOMYELINASE DEFICIENCY NIEMANN-PICK DISEASE, INTERMEDIATE, PROTRACTED NEUROVISCERAL, INCLUDED
Number of Symptoms 46
OrphanetNr: 77292
OMIM Id: 257200
ICD-10: E75.2
UMLs: C0268242
MeSH: D052536
MedDRA:
Snomed: 52165006

Prevalence, inheritance and age of onset:

Prevalence: 0.25 of 100 000 [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Metabolic disease with macular cherry-red spot
 -Rare eye disease
 -Rare genetic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Sphingolipidosis
 -Rare genetic disease
Sphingolipidosis with epilepsy
 -Rare neurologic disease

Comment:

Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1) (PMID:25987176).

Symptom Information: Sort by abundance 

1
 (HPO:0001114) Xanthelasma 13 / 7739
2
 (HPO:0010729) Cherry red spot of the macula typical [HPO] frequent [IBIS] 25987176 IBIS 10 / 7739
3
 (HPO:0001257) Spasticity 251 / 7739
4
 (HPO:0001265) Hyporeflexia 208 / 7739
5
 (HPO:0001315) Reduced tendon reflexes 160 / 7739
6
 (HPO:0001263) Global developmental delay 853 / 7739
7
 (HPO:0001284) Areflexia 198 / 7739
8
 (HPO:0001249) Intellectual disability 1089 / 7739
9
 (HPO:0002063) Rigidity 92 / 7739
10
 (HPO:0002305) Athetosis 31 / 7739
11
 (HPO:0002344) Progressive neurologic deterioration Frequent [IBIS] 25987176 IBIS 27 / 7739
12
 (HPO:0001270) Motor delay 322 / 7739
13
 (HPO:0000939) Osteoporosis 129 / 7739
14
 (HPO:0002013) Vomiting 191 / 7739
15
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
16
 (HPO:0001538) Protuberant abdomen 36 / 7739
17
 (HPO:0006579) Prolonged neonatal jaundice 25 / 7739
18
 (HPO:0001433) Hepatosplenomegaly Very frequent [IBIS] 25987176 IBIS 78 / 7739
19
 (HPO:0002019) Constipation 194 / 7739
20
 (HPO:0002240) Hepatomegaly 467 / 7739
21
 (HPO:0011968) Feeding difficulties 240 / 7739
22
 (HPO:0001744) Splenomegaly 337 / 7739
23
 (HPO:0001508) Failure to thrive Very frequent [IBIS] 25987176 IBIS 454 / 7739
24
 (HPO:0001510) Growth delay 295 / 7739
25
 (HPO:0004322) Short stature 1232 / 7739
26
 (HPO:0004325) Decreased body weight 492 / 7739
27
 (HPO:0000991) Xanthomatosis 16 / 7739
28
 (HPO:0001039) Atheroeruptive xanthoma 9 / 7739
29
 (HPO:0003609) Foam cells with lamellar inclusion bodies 4 / 7739
30
 (HPO:0001982) Sea-blue histiocytosis 7 / 7739
31
 (HPO:0001935) Microcytic anemia 32 / 7739
32
 (HPO:0004333) Bone-marrow foam cells 11 / 7739
33
 (HPO:0002205) Recurrent respiratory infections 254 / 7739
34
 (HPO:0011947) Respiratory tract infection 28 / 7739
35
 (HPO:0002207) Diffuse reticular or finely nodular infiltrations 11 / 7739
36
 (HPO:0008940) Generalized lymphadenopathy 14 / 7739
37
 (HPO:0002716) Lymphadenopathy 129 / 7739
38
 (HPO:0010547) Muscle flaccidity 466 / 7739
39
 (HPO:0001324) Muscle weakness 859 / 7739
40
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
41
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] 25987176 IBIS 990 / 7739
42
 (OMIM) Cherry-red maculae (50%) 3 / 7739
43
 (OMIM) Multiple organs (lung, liver, spleen, kidney, brain) contain foamy resident cells and histiocytes 1 / 7739
44
 (OMIM) Decreased acid sphingomyelinase activity 3 / 7739
45
 (OMIM) Gray, granular-appearing maculae 1 / 7739
46
 (OMIM) Electron microscopy of foam cells shows lamellar inclusions 3 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM In Niemann-Pick disease, lipid, mainly sphingomyelin, accumulates in reticuloendothelial and other cell types throughout the body. The accumulation in ganglion cells of the central nervous system leads to cell death. Crocker and Farber (1958) presented a detailed clinical ...
Genotype-Phenotype Correlations OMIM Takahashi et al. (1992) concluded that small deletions or nonsense mutations that result in truncated ASM polypeptide and missense mutations that render the enzyme noncatalytic cause type A Niemann-Pick disease, whereas missense mutations that produce a defective enzyme ...
Molecular genetics OMIM Levran et al. (1991) identified a point mutation in the SMPD1 gene (607608.0001) in an Ashkenazi Jewish patient with type A Niemann-Pick disease. Takahashi et al. (1992) characterized 3 SMPD1 mutations (607608.0005-607608.0007) causing Niemann-Pick disease type A. Ida ...
Population genetics OMIM Despite considerable uncertainty about the demographic history of Ashkenazi Jews and their ancestors, Slatkin (2004) considered available genetic data to be consistent with a founder effect resulting from a severe bottleneck in population size between 1100 A.D. and ...