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Gaucher Disease & Acid Sphingomyelinase Deficiency

About Gaucher disease and Acid Sphingomyelinase Deficiency (ASMD or Niemann-Pick A/B)

Gaucher disease and acid sphingomyelinase deficiency (ASMD, Niemann-Pick A and B) are rare autosomal recessive lysosomal enzyme deficiency disorders with phenotypic overlap. Both diseases are due to genetic mutations that result in enzyme deficiency and a subsequent accumulation of lysosomal material in the cells of the macrophage/monocyte lineage.1-3

Gaucher disease is caused by a deficiency in glucocerebrosidase (GBA) enzyme activity, encoded by the GBA gene.1 Deficiency or absence of this enzyme leads to a build-up of glycosylceramide (Gl1) and glucosylsphingosine (LysoGl1, LysoGb1) in macrophage lysosomes (Gaucher cells), giving them a crinkled tissue paper appearance.

ASMD is caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene that results in deficiency of the enzyme acid sphingomyelinase (ASM) and a subsequent accumulation of sphingomyelin and other lipids in cells, giving them a characteristic foamy appearance (Niemann-Pick cells).1, 3-5

Cellular substrate accumulation eventually leads to tissue and organ damage and both diseases present with similar symptoms: anemia, thrombocytopenia, splenomegaly, and bone involvement such as bone pain, osteopenia, osteonecrosis, and fractures.1 Both diseases have a wide phenotypic spectrum with severe neuronopathic forms and chronic visceral forms. ASMD also has an intermediate chronic neurovisceral form. Some symptoms differ between diseases: skin manifestations, an atherogenic dyslipidemia, and pulmonary involvement (interstitial lung disease) is more commonly associated with ASMD, whereas musculoskeletal involvement is specific to Gaucher disease.2, 5, 6

This testing service has not been cleared or approved by the U.S. Food and Drug Administration. Testing services may not be licensed in accordance with the laws in all countries. The availability of specific test offerings is dependent upon laboratory location. The content on this page is provided for informational purposes only, not as medical advice. It is not intended to substitute the consultation, diagnosis, and/or treatment provided by a qualified licensed physician or other medical professionals.

Gaucher Disease & Acid Sphingomyelinase Deficiency

Prevalence of Gaucher disease Type 1 (non-neuronopathic): 1 in 50,000-100,000 in the general population, worldwide;7 and approximately 1 in 350-450 people of Ashkenazi Jewish heritage8. The incidence of ASMD is estimated at 0.5 per 100,000 births.2

Program eligibility

The Roadmap2Rare Diagnostic Program* consists of parallel testing of both glucocerebrosidase and acid sphingomyelinase (ASM) enzyme assays with reflex to DNA sequencing of GBA or SMPD1 as appropriate, for individual patients with:

  • Symptoms suggestive of Gaucher disease or ASMD
  • Presumptive positive newborn screens for either disorder

*This testing program is not appropriate for carrier testing. 

About the test
  • Glucocerebrosidase enzyme assay (includes ASM enzyme assay in parallel) and if deficient will reflex to,
  • GBA sequencing and Lyso-GL1 or SMPD1 sequencing as appropriate
  • If either enzyme assay or GBA/SMPD1 sequencing has already been performed, these tests can be ordered individually, if needed.

1. Baris HN, Cohen IJ, Mistry PK. Gaucher disease: the metabolic defect, pathophysiology, phenotypes and natural history. Pediatr Endocrinol Rev. 2014;12:72-81.

2. McGovern MM, Avetisyan R, Sanson BJ, Lidove O. Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017;12(1):41.

3. Wasserstein MP, Schuchman EH. Acid sphingomyelinase deficiency. NCBI GeneReviews (2015). Available at: Accessed July 19, 2018.

4. Kaplan P, Andersson HC, Kacena KA, et al. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med. 2006;160:603-608.

5. McGovern MM, Dionisi-vici C, Giugliani R, et al. Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency. Genet Med. 2017;19(9):967-974.

6. Simpson WL, Hermann G, Balwani M. Imaging of Gaucher disease. World J Radiol. 2014;6:657-668.

7. Mistry PK, Cappellini MD, Lukina E, et al. Consensus conference: a reappraisal of Gaucher disease – diagnosis and disease management algorithms. Am J Hematol. 2011;86(1):110-5.

8. Bronstein S, Karpati M, Peleg L. An update of Gaucher mutations distribution in the Ashkenazi Jewish population: prevalence and country of origin of the mutation R496H. Isr Med Assoc J. 2014;16:683-685.