Masks for a rare pathology: A clinical case of lysosomal acid lipase deficiency with asymptomatic onset and delayed verification of diagnosis

Lysosomal acid lipase deficiency (LALD, cholesterol ester storage disease, OMIM #278000) is a rare autosomal recessive disorder resulting from underlying LIPA gene mutations, leading to impaired hydrolysis of cholesterol esters and triglycerides within lysosomes. Common presenting symptoms include hepatomegaly, dyslipidemia, increased transaminases, steatosis, and in severe forms – progressive liver fibrosis and early atherosclerosis. The presented clinical case describes the management of LALD in an 8-year-old girl, characterized by early age onset, absence of typical delay in physical development and pronounced polymorphism of clinical manifestations. For several years, gastrointestinal symptoms combined with anemia, nosebleeding, and fatigue, which were evaluated as functional disorders prevailed. The diagnostic search was initiated late, despite the presence of hepatomegaly, persistent hypercholesterolemia, and elevated transaminases. The diagnosis was verified based on decreased enzymatic activity of lysosomal acid lipase and results of the molecular genetic analysis (variant c.894G>A in the LIPA gene in the homozygous state). Liver steatosis and fibrosis progression was observed in the absence of timely initiation of enzyme replacement therapy. A clinical example demonstrates the difficulties of early diagnosis of lysosomal storage diseases in pediatric practice. The case highlights the diagnostic challenges due to phenotypic variability and clinical similarities with more common disorders, including familial hypercholesterolemia. The article discusses differential diagnostic approaches, including exclusion of viral hepatitis, Wilson's disease, autoimmune liver diseases, and hereditary metabolic diseases. The need for early diagnosis, family screening and optimization of access to enzyme replacement therapy has been underlined. The article also outlines promising directions in the development of neonatal screening programs and areas of targeted therapy, including gene technologies. This case emphasizes the need to increase the alertness of clinicians and introduce systemic diagnostic algorithms into clinical practice.