Lysosomal acid lipase deficiency (LALD) is a rare genetic disease characterized by the accumulation of cholesteryl esters and triglycerides in many organs, including the liver, spleen, lymph nodes, bone marrow, and vascular endothelium. Patients with LALD can appear asymptomatic until liver failure or premature sudden death from coronary artery disease, stroke, and aneurysm, which lead to the diagnosis. Herein, we present a diagnostic workup in a young 17-year-old female patient who manifested hepatosplenomegaly, elevated liver enzymes, severe dyslipidemia, and systemic atherosclerosis. Liver biopsy demonstrated over 90% diffuse microvesicular steatosis, lipid accumulation in Kupffer cells, and birefringent cholesteryl ester crystals. The diagnosis of LALD was proven by the decrease of lysosomal acid lipase activity in dried blood spots and by the detection of two compound heterozygous mutations in the LIPA gene: nonsense mutation G796T (Gly266Term) and splicing site mutation G894A (E8SJM). The patient started enzyme replacement therapy with sebelipase alfa. Following the 1-year treatment, the patient remained asymptomatic, her serum aminotransferase levels were normal, liver density increased due to lipid resorption, and plaque-associated stenosis of carotid artery regressed. Moreover, liver biopsy showed a decrease of cholesteryl ester crystals in Kupffer cells.
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