Lipid Storage Disorder: Lysosomal Acid Lipase (LAL) Deficiency

I. Pathogenesis

Caused by deficiency of lysosomal acid lipase (LAL) due to mutations in the LIPA gene
Leads to accumulation of cholesteryl esters and triglycerides in organs, damaging cells and tissues
Two clinical forms:
- Wolman disease: severe, infantile-onset
- Cholesteryl Ester Storage Disease (CESD): milder, later-onset

II. Clinical Features

Wolman Disease

Fatal by age 1
Massive organomegaly, mental deterioration
Distended abdomen, steatorrhea, vomiting
Jaundice, anemia
Calcium deposits in adrenal glands

CESD

Variable progression; may lead to cirrhosis
Hypercholesterolemia and risk of atherosclerosis
Chronic liver disease

III. Diagnosis

Measurement of LAL enzyme activity in blood or liver tissue
LIPA gene sequencing
Liver biopsy findings:
- Lipid in membrane-bound vesicles (lysosomes)
- H&E stain: pale, vacuolated hepatocytes
- PAS stain: diastase-resistant residual bodies
- Polarized light: cholesterol ester crystals

IV. Treatment & Management

Dietary and pharmacologic treatment of hyperlipidemia (e.g., statins, cholestyramine)
Monitoring and management of liver fibrosis or cirrhosis
Liver transplantation in advanced cases

LAL Deficiency: Wolman Disease vs CESD
Feature	Wolman Disease	CESD
Onset	Infancy (within first months)	Childhood to adulthood
Severity	Severe; fatal by age 1	Milder; variable progression
Organ Involvement	Liver, spleen, adrenal glands	Primarily liver
Key Symptoms	Steatorrhea, vomiting, anemia, adrenal calcifications	Hypercholesterolemia, risk of atherosclerosis
Liver Biopsy Findings	Lipid in lysosomes; cholesterol crystals	Similar lysosomal lipid accumulation
Treatment	Supportive; no curative therapy	Lipid-lowering therapy; liver transplant if needed