Niemann-Pick Disease Types A & B
Niemann-Pick Disease (NPD) Types A & B are the neuronopathic and non-neuronopathic forms of an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme acid sphingomyelinase (ASM).
PrintNiemann-Pick Disease (NPD) Types A & B are the neuronopathic and non-neuronopathic forms of an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme acid sphingomyelinase (ASM).
Mutations in SMPD1 gene cause both the severe, early onset Type A disease and the milder Type B. Niemann-Pick Disease Types A & B are more common in the Ashkenazi Jewish population.
The Ambry Test: Niemann-Pick Disease Types A & B is a full Gene Sequence Analysis that detects about 99% of described mutations in SMPD1. Sequence analysis of SMPD1 detects mutations in greater than 95% of patients with enzymatically confirmed ASM deficiency. Testing is appropriate for diagnostic confirmation or high-risk carrier screening. Carrier screening for the four NPD Type A mutations that are most common in the Ashkenazi Jewish population is also available as part of Ambry's Ashkenazi Jewish FlexPanel. Please see the entry for Ashkenazi Jewish FlexPanel under the Panels menu for more information.
Acid sphingomyelinase deficiency, which includes Niemann-Pick Disease (NPD) Types A & B, is an autosomal recessive disease caused by the deficiency of acid sphingomyelinase (ASM) activity. ASM is found in lysosomes, where lipid metabolism breaks down and transport fats and cholesterol in the body. Mutations on the SMPD1 gene cause harmful build up of lipids in the cells of the body, including the spleen, liver, bone marrow and brain. The two main forms of Niemann-Pick disease are Types A and B. Type A is a severe early-onset form, with rapid neurodegeneration that usually leads to death by three years of age. Symptoms include hepatosplenomegaly, developmental delay, interstitial lung disease, and cherry-red spots of the retinal maculae. Type B is a milder, non-neurological form with later onset, and patients may survive into adulthood. Symptoms of NPD Type B include hepatosplenomegaly, interstitial lung disease, hyperlipidemia, and thrombocytopenia.1 NPD occurs in 1 in 264,000 births,2 however, this disease is more common in the Ashkenazi Jewish population, with an incidence of 1 in 40,000 and a carrier rate of 1 in 90.3 There is no effective treatment for NPD, and management includes treatment of symptoms and supportive care.4,5
NPD cannot be diagnosed solely on clinical grounds. The diagnosis of acid sphingomyelinase deficiency requires measurement of acid sphingomyelinase (ASM) enzyme activity in peripheral blood lymphocytes or cultured skin fibroblasts. Molecular genetic testing can confirm the diagnosis of NPD if both disease-causing alleles are identified, but should not be used in place of biochemical testing. There are over 100 disease causing mutations, including point mutations, deletions and splicing abnormalities.6 Testing should be considered in those suspected to have NPD based on clinical symptoms, and for carrier testing in high-risk individuals, such as those with a family history of NPD and/or those of Ashkenazi Jewish background.
This Ambry Test is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-6 of the SMPD1 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis for individual SMPD1 mutations known to be in the family is also available.
Sequence analysis of SMPD1 detects about 99% of described mutations in SMPD1, and detects mutations in greater than 95% of patients with enzymatically confirmed ASM deficiency.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1860 | SMPD1 Gene Sequence Analysis | 83891x1, 83894x10, 83898x9, 83904x18, 83909x18, 83912x1 |
| Technique | Days |
|---|---|
| SMPD1 Gene Sequence Analysis | 10-21 |
1 Schuchman EH. J Inherit Metab. 2007;30:654-663.
2 Meikle PJ, Hopwood JJ, Clague AE, Carey WF. JAMA. 1999;281:249–54.
3 Schuchman EH, Miranda SR. Genet Test. 1997;1:9-13.
4 National Institute of Neurological Disorders and Stroke information page. http://www.ninds.nih.gov/disorders/niemann/ niemann.htm. Accessed October 28, 2008.
5 McGovern MM,Wasserstein MP, Giugliani R, et al. Pediatrics. 2008;122(2):341-349.
6 Schuchman EH, Suchi M,Takahashi T, et al. J Biol Chem. 1991;266:8531-8539.