Lysosomal Acid Lipase Deficiency in Risk Groups

Inclusion Criteria Age 12 months to 18 years (infantile form is out of scope for the analytical component); Patients not previously evaluated for LAL-D (test-naïve); Presence of at least one (1) of the following major criteria: Unexplained hepatomegaly and/or splenomegaly persisting ≥3 months; Persistent hypertransaminasemia: ALT or AST ≥ 1.5× upper limit of normal (ULN) after exclusion of common metabolic/infectious causes; Atherogenic dyslipidemia: elevated total cholesterol (TC), elevated LDL-C and/or reduced HDL-C (LDL-C \>95th percentile for age and sex or HDL-C \<5th percentile); triglycerides not markedly elevated. Presence of at least two (2) of the following minor criteria: Chronic diarrhea or intermittent unstable bowel movements; Abdominal pain and/or bloating; Loss of appetite; Nausea, vomiting; Belching, heartburn; Weight loss, growth deceleration (height/weight lag behind peers); Weakness, easy fatigability; Recurrent aphthous stomatitis (oral mucosal ulcers); Splenomegaly (if not counted as a major criterion); Anemia and/or thrombocytopenia; Evidence of steatosis/fibrosis by ultrasound/elastography/ liver examination by MRI; Suboptimal response to lipid-lowering therapy: after ≥3 months of optimized therapy (maximally tolerated statin ± ezetimibe with documented adherence), LDL-C reduction \<50% from baseline OR on-treatment LDL-C remains above guideline targets (e.g., ≥3.4 mmol/L without very high risk or ≥2.6 mmol/L in very-high-risk settings), despite therapy \[12\]. Family history of FH-like dyslipidemia without typical FH genetic markers (if available). Provision of signed and dated written informed consent by parent(s)/legal guardian(s) (and the child, where applicable). Exclusion Criteria Confirmed alternative etiology fully explaining liver disease/dyslipidemia (e.g., hepatitis A/B/C, autoimmune hepatitis by diagnostic criteria) without grounds to suspect LAL-D; Wolman disease; Long-term use of systemic corticosteroids which is defined as oral or parenteral continuous administration during ≥14 days in the last 6 months prior to the inclusion.