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).