Real-World Experience from Türkiye: Genetic and Therapeutic Insights in Pediatric Heterozygous Familial Hypercholesterolemia.

Objective: Familial hypercholesterolemia (FH) is an inherited metabolic disorder that increases cardiovascular risk from childhood. Despite its frequency, pediatric diagnosis and treatment remain inadequate, particularly in developing countries.

Methods: We retrospectively analysed 124 pediatric patients with genetically confirmed heterozygous FH (HeFH). Genetic testing included sequencing of LDLR, APOB, and PCSK9. We assessed clinical features, treatment responses, statin use, and adverse events. A comparative analysis was conducted between different statin types.

Results: Only 28.2% of patients were diagnosed via routine lipid screening, though 90.3% had a positive family history. After diagnosis, 16.1% declined treatment and 41.1% were lost to follow-up. Most genetic diagnoses involved pathogenic LDLR variants; a few cases involved APOB and PCSK9. We identified three novel LDLR variants. Among treated patients, atorvastatin led to a greater median LDL-C reduction. A higher (though not statistically significant) proportion of pitavastatin users reached LDL-C targets. LDL-C reduction was positively correlated with baseline LDL-C levels. For the majority of patients, statins were well tolerated; five patients had transient creatine kinase (CK) elevations that resolved with treatment interruption.

Conclusion: This is the first large pediatric HeFH cohort study from Turkey providing details on both genetic background and treatment outcomes. Despite genetic confirmation, significant gaps remain in early diagnosis, treatment acceptance, and long-term follow-up. Both atorvastatin and pitavastatin proved to be safe and effective. Findings emphasise the need for national screening programmes, family education, dietary counselling, and consistent follow-up.