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}