The role of lysosomal acid lipase deficiency in dyslipidemia and liver disorders.

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene, leading to reduced lysosomal acid lipase activity, cholesterol ester accumulation, and systemic manifestations including liver dysfunction and dyslipidemia. We report the case of a 25-year-old male presenting with subacute jaundice, hyperbilirubinemia (total bilirubin 51 mg/dL, predominantly direct), and dyslipidemia characterized by elevated total cholesterol and low HDL cholesterol levels. Initial diagnostic workup for acute hepatitis and liver dysfunction, including serological and imaging studies, was unremarkable. Liver biopsy revealed canalicular cholestasis and T-lymphocyte infiltration without fibrosis, raising suspicion for a metabolic or genetic etiology. Genetic analysis confirmed a heterozygous pathogenic mutation (c.894 G>A) in the LIPA gene, establishing the diagnosis of CESD. The patient required advanced management with a molecular adsorbent recirculating system to address refractory hyperbilirubinemia. CESD often mimics other metabolic and hepatic conditions, such as familial hypercholesterolemia or non-alcoholic fatty liver disease, necessitating high clinical suspicion and genetic confirmation for diagnosis. This case underscores the importance of recognizing CESD in patients with atypical dyslipidemia and persistent hepatic abnormalities, as early identification enables targeted therapeutic interventions, including Sebelipase alfa enzyme replacement therapy.