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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.

• Saint Petersburg, Russia
• Samara, Russia