Endocrine Abstracts

Introduction: Familial hypercholesterolaemia (FH) has a gene frequency of at least 1/500 with >80% those affected remaining unidentified. Affected individuals have elevated LDL levels from birth which is a major cause of treatable premature coronary artery disease. NICE guidance recommends statin treatment from the age of 10 yrs for children with a confirmed diagnosis of FH. We were the first centre in England to have commissioned contact tracing and cascade testing to confirm the diagnosis of FH. Previously the genetic test for the common mutations (FH20) was only 50% sensitive. New next generation sequencing techniques are >90% sensitive. We describe biochemical and genetic characteristics of 36 children with confirmed FH, and the safety and efficacy of early atorvastatin treatment.

Methods: All children with a clinical or genetic diagnosis of were offered lifestyle advice, dietetic review, consultation with specialist genetic counsellors, specialist paediatric follow-up and fasted lipid profiles. Genetic investigations included FH20, NGS and cascade testing (direct gene sequencing for known mutation in relative).

Results: 20/36 had previously had FH20 testing (13 mutations identified). A further 11 mutations were identified using NGS and ten using cascade testing. 25 mutations were LDL-R, 9:ApoB, 1: mutation negative, 1: unknown variant. 28/36 were on Atorvastatin at doses of 10 mg (n=14), 20 mg (n=13) and 40 mg (n=1). Mean (range) age at onset of treatment was 10.1 (0.1–16.0). Mean (S.D.) BMISDS was 0.48 (1.27). Mean (S.D.) LDL pre-treatment vs post-treatment was 5.3 (1.3) vs 3.0 (0.6) mmol/l, (P<0.001). The 50th percentile LDL for the normal population at this age is 2.25 mmol/l. There were no side effects, CK or LFT abnormalities related to statin treatment.

Conclusions: Contact tracing and cascade testing with NGS is highly effective in identifying children with FH. Early data suggests atorvastatin treatment is safe and effective from the age of 10 yrs but further data is required to establish long term safety and improved cardiovascular outcomes children.