Lysosomal Acid Lipase Deficiency
Conditions
Brief summary
A multicenter real-world observational study of the prevalence, diagnostic pathways, and clinical characteristics of lysosomal acid lipase deficiency in pediatric and adolescent risk groups in the Russian Federation (HELIOS)
Interventions
None listed
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To estimate the proportion of patients with genetically confirmed LAL-D (defined by decreased LAL activity plus presence of biallelic pathogenic LIPA variants) among 12-month-to-18-year-old patients identified by predefined red flags. | Day 60 (Visit 2) | To achieve the primary objectives of the study the following baseline clinical and demographic characteristics of patients will be collected or evaluated. Proportion (%), with 95% confidence interval, of patients with genetically confirmed LAL-D among screened participants (confirmation by LIPA sequencing following detection of decreased LAL activity in DBS) |
Countries
Russia
Outcome results
None listed