Niemann-Pick disease type B

General Information (adopted from Orphanet):

Synonyms, Signs: NIEMANN-PICK DISEASE, INTERMEDIATE, WITH VISCERAL INVOLVEMENT AND RAPID PROGRESSION, INCLUDED
NIEMANN-PICK DISEASE, TYPE F, INCLUDED
Number of Symptoms 22
OrphanetNr: 77293
OMIM Id: 607616
ICD-10: E75.2
UMLs: C0268243
MeSH: D052537
MedDRA:
Snomed: 39390005

Prevalence, inheritance and age of onset:

Prevalence: 0.4 of 100 000 [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Rare hereditary metabolic disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease
Secondary interstitial lung disease specific to childhood associated with a metabolic disease
 -Rare respiratory disease
Sphingolipidosis
 -Rare genetic 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:0001103) Abnormality of the macula 7 / 7739
2
 (HPO:0001433) Hepatosplenomegaly Very frequent [IBIS] 25987176 IBIS 78 / 7739
3
 (HPO:0002240) Hepatomegaly 467 / 7739
4
 (HPO:0001744) Splenomegaly 337 / 7739
5
 (HPO:0004322) Short stature 1232 / 7739
6
 (HPO:0003609) Foam cells with lamellar inclusion bodies 4 / 7739
7
 (HPO:0001982) Sea-blue histiocytosis 7 / 7739
8
 (HPO:0004333) Bone-marrow foam cells 11 / 7739
9
 (HPO:0002155) Hypertriglyceridemia 67 / 7739
10
 (HPO:0003233) Hypoalphalipoproteinemia 18 / 7739
11
 (HPO:0003141) Hyperbetalipoproteinemia 10 / 7739
12
 (HPO:0002205) Recurrent respiratory infections 254 / 7739
13
 (HPO:0002207) Diffuse reticular or finely nodular infiltrations 11 / 7739
14
 (HPO:0002094) Dyspnea 132 / 7739
15
 (HPO:0011947) Respiratory tract infection 28 / 7739
16
 (OMIM) Electron microscopy of foam cells shows lamellar inclusions 3 / 7739
17
 (OMIM) Decreased platelets 2 / 7739
18
 (OMIM) Cherry-red maculae (50%) 3 / 7739
19
 (OMIM) Decreased pulmonary diffusion secondary to alveolar infiltration 2 / 7739
20
 (OMIM) Decreased acid sphingomyelinase activity 3 / 7739
21
 (OMIM) Multiple visceral organs (lung, liver, spleen, kidney) contain foamy resident cells and histiocytes 2 / 7739
22
 (OMIM) Absence of neurologic manifestations 2 / 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 ...
Diagnosis OMIM Simonaro et al. (2002) commented that type B Niemann-Pick disease is a particularly difficult disorder to diagnose clinically. They suggested that it might be useful to screen in heart disease clinics for patients with very low HDL cholesterol ...
Clinical Description OMIM In contrast to patients with Niemann-Pick disease type A, patients with type B have involvement of the spleen, liver, and lungs, and remain free of neurologic manifestations despite the massive visceral involvement. Patients with type B often survive ...
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 In an Ashkenazi Jewish patient with Niemann-Pick disease type B, Levran et al. (1991) identified a mutation in the acid lysosomal sphingomyelinase phosphodiesterase-1 gene (607608.0002). Takahashi et al. (1992) identified 3 SMPD1 mutations (607608.0008-607608.0009) causing Niemann-Pick disease type ...
Population genetics OMIM Simonaro et al. (2002) collected demographic and/or mutation information on a worldwide sample of 394 patients with type B Niemann-Pick disease. They found that the disorder is panethnic, with the highest incidence occurring in individuals of Turkish, Arabic, ...