ESPE Abstracts

Introduction: Lysosomal Acid Lipase Deficiency (LAL-D) is a rare and systemic condition, secondary to LIPA gene mutations, responsible for lysosomal accumulation of cholesterol esters and triglycerides. Clinical manifestations are heterogeneous in terms of age of onset, severity and biochemical and radiological findings. Dyslipidemia, hepatomegaly and hepatosteatosis with hypertransaminasemia are the most common features. There is significant evidence of increased risk of premature atherosclerosis and cardiovascular disorders related to the alteration of lipid profile. This case report documents the difficulty in diagnosing LAL-D especially in the context of common clinical pictures associated with obesity-related metabolic syndrome.

Case report: F. is a 12-year-old child in follow-up for obesity (weight 83 kg, height 164 cm, BMI 30.8 kg/m2, BMIz +2.94), metabolic syndrome, severe hepatosteatosis and familial hypercholesterolemia (total cholesterol 265 mg/dl, LDL-C 191 mg/dl, HDL-C 27 mg/dl) related to LDLR (low density lipoprotein receptor) gene heterozygous mutation, in dietary-nutritional and pharmacological treatment with pravastatin. Father with ill-defined liver cirrhosis awaiting transplant. In the suspicion of hypertransaminasemia (AST 60 U/l, ALT 129 U/L) secondary to statin toxicity, this therapy was temporarily suspended. Clinical picture substantially unchanged after 6 months, with persistently elevated transaminases (AST 55 U/l, ALT 144 U/L), appeared compatible with MAFLD (metabolic associated fatty liver disease) aggravated by the condition of familial hypercholesterolemia. The persistence of hypertransaminasemia during observation time, the familiarity for evolutive liver diseases and the severity of steatosis documented by ultrasound, required the exclusion of other causes of liver disease (infectious, autoimmune, metabolic/genetic, nutritional/intestinal, toxic, muscular). In particular, the coexistence of hypertransaminasemia (ALT >1.5 nv), dyslipidemia (LDL> 190 mg/dl, HDL <40 mg/dl) and hepatosteatosis suggested the diagnostic suspicion of LAL-D. Enzyme activity was reduced in dried blood spot (DBS) screening test, so molecular testing was performed to look for mutations in the LIPA gene, which is currently underway.

Conclusion: Although signs and symptoms common to other diseases make identification challenge, LAL-D should be considered in the differential diagnosis of familial forms of dyslipidemia, metabolic syndromes with hepatosteatosis and hypertransaminasemia and pediatric diseases presenting with dyslipidemia and liver storage of intracellular products. The trend, variably progressive, leads to fibrosis, cirrhosis and liver insufficiency. The current availability of DBS screening test may consent an early identification of LAL-D and an improved prognosis thanks to possibility of enzyme replacement therapy with sebelipase alfa to improve lipid profile, liver enzymes and hepatomegaly.