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 is more commonly associated with ASMD, whereas musculoskeletal involvement is specific to Gaucher disease.2, 5, 6
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
The Lantern Project* offers parallel testing of both 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 as enzyme assay will not reliably detect carriers
β-glucosidase and Acid Sphingomyelinase Enzyme Assays, Lyso-GB1
- Dried blood spots are preferred, but whole blood is also acceptable.
SMPD1 and GBA Gene Sequencing
- Dried blood spots (DBS) are preferred, but whole blood is also acceptable. A saliva sample can be used if only gene sequencing is being ordered.
Bundled Testing (Enzyme assay with reflex to sequencing and biomarker)
- Dried blood spots (DBS) are preferred, but whole blood is also acceptable. A saliva sample cannot be used for enzyme assay or biomarker measurement.
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