Two cases of late-onset lysosomal acid lipase deficiency with Achilles tendon thickening

Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease, classified into early-onset form and late-onset form. Late-onset LAL-D is characterized by dyslipidemia resembling familial hypercholesterolemia (FH), often leading to diagnostic challenges. Achilles tendon (AT) thickening is a well-known physical hallmark of FH, whereas it has not previously been reported in late-onset LAL-D. We report 2 cases of late-onset LAL-D in young women who exhibited AT thickening in ultrasonography. Both patients demonstrated markedly elevated low-density lipoprotein cholesterol levels and reduced lysosomal acid lipase activity, with pathogenic lipase A lysosomal acid type gene variants confirming the diagnosis of late-onset LAL-D. Ultrasonographic evaluation revealed AT thickening meeting the Japanese Atherosclerosis Society criteria for FH, with homogeneous internal tendon structures lacking hypoechoic areas or calcification. Notably, the internal echogenicity differed from that typically observed in FH, suggesting distinct underlying lipid deposition patterns. Late-onset LAL-D leads to intracellular accumulation of cholesterol esters and triglycerides within lysosomes, whereas FH is characterized by both intracellular lipid accumulation within macrophage foam cells and extracellular lipid deposition. These differences may account for the distinct ultrasonographic appearances of the AT observed in late-onset LAL-D compared with FH. This is the first report of AT thickening in patients with late-onset LAL-D. Our findings suggest that late-onset LAL-D should be included in the differential diagnosis when AT thickening is observed in patients with dyslipidemia. The combined assessment of AT ultrasonography and lipid profiles may enable accurate differentiation between late-onset LAL-D and FH, thereby facilitating early and appropriate diagnosis and management.