Acid sphingomyelinase deficiency and Gaucher disease in adults: Similarities and differences in two macrophage storage disorders

The lysosomal storage diseases chronic visceral acid sphingomyelinase deficiency (ASMD) and Gaucher disease type 1 (GD1) are both macrophage storage disorders with overlapping clinical manifestations. We compared cross-sectional data on visceral, hematological, and biochemical manifestations of untreated adult patients with chronic visceral ASMD (n = 19) and GD1 (n = 85). Spleen volume, liver volume, and bone marrow fat fraction did not significantly differ between the two disease groups (p >0.05 for all). Chitotriosidase activity was higher in GD1 (GD1: median 30 940 nmol/(mL.h), range 513–201 352, ASMD: median 1693 nmol/(mL.h), range 326–6620, p <0.001), whereas platelet levels were lower (GD1: median 102 10⁹/L, range 16–726, ASMD: median 154 10⁹/L, range 86–484, p <0.010), as were hemoglobin levels (GD1: median 7.8 mmol/L, range 5.0–10.4, ASMD: median 9.0 mmol/L, range 7.0–10.4, p <0.001). No bone complications were reported for ASMD, compared to 33% in GD1 (p <0.005). In ASMD pulmonary disease was more severe as evidenced by a median diffusion capacity of the lungs for carbon monoxide of 73% of predicted (range 26–104), compared to 85% (range 53–126) in GD1 (p = 0.029). In conclusion, bone complications, hematological abnormalities, chitotriosidase activity, and CCL18 levels were more prominent in GD1, while pulmonary manifestations were more common in AMSD. Different secondary pathophysiological processes surrounding sphingomyelin and glucosylceramide accumulation might explain these differences.