Detecting lysosomal acid lipase deficiency in children and teens at risk

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)

This project will test how common lysosomal acid lipase deficiency is and how it is diagnosed in children and adolescents in Russia who have unexplained liver enlargement, abnormal liver enzymes, or unusual cholesterol levels.

Quick facts

• Study type: Observational
• Enrollment: 1200 (estimated)
• Sex: All
• Sponsor: AstraZeneca (industry)
• Locations: 2 sites (Nizhny Novgorod and 1 other locations)
• Trial ID: NCT07455864 on ClinicalTrials.gov

What this trial studies

This is a multicenter, real-world observational project in the Russian Federation enrolling patients aged 12 months to 18 years who have not previously been evaluated for LAL‑D and who meet specified clinical risk criteria. Participating sites in Nizhny Novgorod and Saint Petersburg will collect clinical histories, laboratory results, and diagnostic-pathway information to determine how often LAL‑D is found in these risk groups and how patients reach a diagnosis. The protocol focuses on patients with at least one major criterion (such as persistent hepatomegaly/splenomegaly, persistent hypertransaminasemia, or atherogenic dyslipidemia) plus at least two minor gastrointestinal or growth-related signs. No investigational treatments are assigned; the study documents real-world diagnostic practice and clinical characteristics to inform improved screening and referral strategies.

Who should consider this trial

Good fit: Children and adolescents aged 12 months to 18 years in Russia who have not been previously tested for LAL‑D and who meet at least one major and two minor clinical criteria are ideal candidates.

Not a fit: Infants under 12 months (the infantile form), patients who have already been evaluated for LAL‑D, or those without the listed risk signs are unlikely to gain benefit from participation.

Why it matters

Potential benefit: If successful, this work could lead to earlier diagnosis and referral for children with LAL‑D, improving management and reducing long-term liver and cardiovascular complications.

How similar studies have performed: Previous screening and observational studies in high-risk groups have identified additional cases of LAL‑D, but comprehensive pediatric real-world data in Russia are limited.

Eligibility criteria

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.

Where this trial is running

Nizhny Novgorod and 1 other locations

• Research site — Nizhny Novgorod, Russia (RECRUITING)
• Research Site — Saint Petersburg, Russia (RECRUITING)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions: Lysosomal Acid Lipase Deficiency