Niemann-Pick Disease Types A and B via the SMPD1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7833 SMPD1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7833SMPD181479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Niemann-Pick Disease (NPD) is one of several disorders of sphingolipid metabolism known as sphingolipidoses. NPD Types A and B (NPD-A and NPD-B) both result from deficient activity of acid-sphingomyelinase (ASM) and subsequent accumulation of sphingomyelin and other lipids in tissues. NPD-A and B are differentiated based on the age of onset, progression and clinical features. NPD-A is a uniformly fatal neurodegenerative disease with onset before the age of 6 months and death by the age of 3 years. The clinical hallmarks of NPD-A are hepatosplenomegaly, cherry-red maculae, failure to thrive, hypotonia, and severe psychomotor retardation. NPD-B is heterogeneous. Symptoms may begin in early childhood or adulthood and progression rate varies among affected individuals, with survival into adulthood. Clinical features of NPD-B may include hepatosplenomegaly, hematological findings, frequent respiratory infections and growth retardation. There is little or no central nervous involvement in NPD-B (Schuchman et al. In: Scriver et al. eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed.:3589–3610, 2001). ASM deficiency affects ~ 1:250,000 individuals (Meikle et al. JAMA 281(3):249-254, 1999). Both forms of the disease arise worldwide with high incidence in individuals of Turkish, Saudi and North African origins; however, the incidence of NPD-A is highest in Ashkenazi Jewish populations (Simonaro et al. Am J Hum Genet 71(6):1413-1419, 2002).

Genetics

NPD-A and B are inherited in an autosomal recessive manner and result from mutations in the SMPD1 gene (Levran et al. Proc Natl Acad Sci USA 88(9):3748-3752, 1991). SMPD1 encodes the ASM, which catalyzes the hydrolysis of sphingomyelin to phosphorylcholine and ceramide. Although over 160 mutations distributed along the gene have been detected in patients with NPD-A and B, four common mutations have been reported. Three of these mutations (Leu304Pro, Arg498Leu and Phe333Serfs*52) account for ~ 95% of patients with NPD-A, and one recurrent mutation, Arg608del, is responsible for most cases of NPD-B of Ashkenazi Jewish origin (Schuchman and Miranda. Genet Test 1(1):13-19, 1997). The majority of mutations are missense. However, nonsense, splicing, small insertions or deletions have been reported. To date, no pathogenic regulatory variants or large deletions have been reported.

Paternal imprinting at the SMPD1 gene has been reported; and heterozygous carrier individuals may therefore develop NPD-B (Simonaro et.al. Am J Hum Genet 78(5): 865-870, 2006).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test detects ~99% of SMPD1 mutations (McGovern, M.M. and Schuchman, E. H. GeneReviews, 2009).

Thus far, no gross deletions or duplications have been reported in SMPD1 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the SMPD1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with NPD-A and NPD-B and heterozygous carrier relatives. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SMPD1.

Gene

Official Gene Symbol OMIM ID
SMPD1 607608
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Interstitial Lung Disease Panel

Citations

  • Human Gene Mutation Database (Bio-base).
  • Levran, O., et.al. (1991). "Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients." Proc Natl Acad Sci U S A 88(9): 3748-3752. PubMed ID: 2023926
  • McGovern, M. M. and Schuchman, E.H. (2009). "Acid Sphingomyelinase Deficiency." GeneReviews. PubMed ID: 20301544
  • Meikle, P. J. et.al. (1999). "Prevalence of lysosomal storage disorders." JAMA 281(3): 249-254. PubMed ID: 9918480
  • Schuchman et al. In: Scriver et al. eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed.:3589–3610, 2001.
  • Schuchman, E. H. and Miranda, S. R. (1997). "Niemann-Pick disease: mutation update, genotype/phenotype correlations, and prospects for genetic testing." Genet Test 1(1): 13-19. PubMed ID: 10464620
  • Simonaro, C. M. et.al. (2006). "Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease." Am J Hum Genet 78(5): 865-870. PubMed ID: 16642440
  • Simonaro, C. M., et.al. (2002). "The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations." Am J Hum Genet 71(6): 1413-1419. PubMed ID: 12369017

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
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Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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