Diagnosis
Gaucher disease and ASMD are rare inherited lysosomal disorders affecting the metabolism of sphingolipids within the lysosome. Both are categorized as rare diseases. The incidence of Gaucher disease is 1 in 50,000 to 1 in 100,000 live births worldwide, and ASMD is estimated to affect 0.5 per 100,000 live births.
Given both conditions are under-recognized, particularly ASMD, and both have several of the same differential diagnoses, it is recommended that patients with clinical suspicion of Gaucher disease also be tested for ASMD.
Enzyme Activity
Gaucher Disease: Glucocerebrosidase enzyme assay:
- Adults: usually 10% to 30% of normal
- Children (severe cases) <10% of normal
- Residual activity does not predict clinical outcome
ASMD: Acid sphingomyelinase enzyme assay:
- <10% residual activity
- Residual activity does not predict clinical outcome
- Consider ordering in parallel, or if glucocerebrosidase is normal
Genetic Testing (DNA Sequencing)
Gaucher Disease: GBA gene sequencing:
- Two pathogenic variants in trans
- Six variants account for 97% of all pathogenic variants in patients of Ashkenazi heritage: N370S, R496H, V394L, 84insG, A→1G+IVS2, and L444P
- N370S is neuroprotective
ASMD: SMPD1 gene sequencing:
- Two pathogenic variants in trans
- ΔR610 is considered to be neuroprotective, common in chronic visceral form in multiple ethnic groups
New to Molecular Testing?
This short video provides general education on molecular testing for healthcare providers who are unfamiliar with the process.
For more information on diagnosing ASMD, including a list of labs offering SMPD1 gene sequencing or acid sphingomyelinase enzyme activity assay, review this short brochure.
References:
McGovern MM, et al. Genet Med. 2017;19(9):967–974. McGovern MM, et al. Orphanet J Rare Dis. 2017;12(1):41. McGovern MM, et al. Pediatrics. 2008;122(2):341–349. Schuchman EH. J Inherit Metab Dis. 2007;30(5):654–663. McGovern MM, et al. Genet Med. 2013;15(8):618–623
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