Lysosomal Acid Lipase Deficiency Presenting as Hepatic Steatosis in a Young Adult
Overview
A 21-year-old male was incidentally found to have massive microvesicular hepatic steatosis with fibrosis during hernia surgery. Subsequent work-up revealed complete lysosomal acid lipase deficiency (LAL-D) due to a homozygous E8SJM mutation, highlighting this rare cause of liver disease.
Background
Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disorder characterized by deficient LAL enzyme activity. Complete deficiency, known as Wolman disease, is fatal in infancy, while partial deficiency (cholesterol ester storage disease) presents in childhood or early adulthood with progressive microvesicular steatosis, fibrosis, and risk of cirrhosis. The disease leads to abnormal cholesterol and triglyceride metabolism, causing orange-colored hepatic steatosis distinct from common fatty liver diseases. Early diagnosis is critical as enzyme replacement therapy with sebelipase alfa is now available.
Data Highlights
Parameter
Value
Normal Range
BMI
20.8 kg/m2
18.5-24.9 kg/m2
Total Cholesterol
265 mg/dL
<200 mg/dL
LDL
211 mg/dL
<130 mg/dL
HDL
39 mg/dL
40-60 mg/dL
Triglycerides
164 mg/dL
<150 mg/dL
ALT
56 IU/L
7-56 IU/L
Serum Ferritin
277 μg/L
24-336 μg/L
LAL Activity
0.0 nmol/3 h
0.1-2.0 nmol/3 h
Key Findings
Incidental discovery of massive microvesicular hepatic steatosis with orange coloration during hernia surgery.
Liver biopsy showed 50–60% microvesicular steatosis with portal, periportal, and septal fibrosis.
Biochemical profile revealed elevated total cholesterol, LDL, triglycerides, and low HDL.
Complete absence of lysosomal acid lipase activity confirmed diagnosis of LAL deficiency.
Homozygous E8SJM (c.894G>A) mutation identified as genetic cause.
LAL-D leads to progressive liver disease and increased cardiovascular risk if untreated.
Clinical Implications
Clinicians should consider LAL deficiency in patients with unexplained microvesicular steatosis and dyslipidemia, especially when liver biopsy shows orange-colored steatosis. Early diagnosis is essential as enzyme replacement therapy with sebelipase alfa can alter disease progression and improve outcomes. Awareness of this rare disorder can prevent misdiagnosis and enable timely intervention.
Conclusion
Lysosomal acid lipase deficiency is a rare but treatable cause of hepatic steatosis and fibrosis in young adults. Recognition of its distinctive clinical, biochemical, and histological features is crucial for early diagnosis and management.
References
Wolman Disease and CESD Overview -- Clinical Features and Outcomes
Lipid Metabolism in LAL Deficiency -- Mechanisms of Dyslipidemia
Sebelipase Alfa Therapy -- Treatment Advances in LAL Deficiency
