SHBC1588

S.PEK¹, S. DISSANAYAKE¹, JIS TANG¹, JKM HOE², WY WAN¹, F SIRAJ¹, ZULKIFLI A¹, MXQ LIN¹, EZL CHAN¹, KAMARUDDIN SNA¹, ETS LIM³, CHUA TSJ³, TAN JL³, LAM CSP³, F YAP⁴, LOH WJ⁵, TAI ES⁶, DRUM CL⁶, RACELL AS⁷, JONNA LBE⁷, DALAN R⁸, ABU BAKAR SZ⁸, YANG L⁸, KOH NSY³, TIONG YS⁹, TAN HC¹⁰, CHEN QF¹⁰, S. TAVINTHARAN²

Khoo Teck Puat Hospital¹, Admiralty Medical Centre², National Heart Centre Singapore³, KK Women’s & Children’s Hospital⁴, Changi General Hospital⁵, National University Hospital⁶, National University of Singapore⁷, Tan Tock Seng Hospital⁸,  Ng Teng Fong General Hospital⁹, Singapore General Hospital¹⁰

Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disease characterized by very high plasma low density lipoproteins cholesterol (LDL-C), increasing the risk for premature cardiovascular disease (CVD) by 20-fold, compared to general population. Prevalence of FH is estimated to be 1 in 250 in the population but only 10% of them are diagnosed. Cascade testing is the most cost-effective method of identifying more individuals with FH. We aim to evaluate the diagnostic yield of cascade screening in patients with genetically confirmed FH.

Probands were recruited based on Simon Broome Criteria from Endocrine and Cardiology clinics at Yishun Health, TTSH, NHGP, NHCS, SGH, CGH, SKH, NUHS and NTFGH. Next generation sequencing was used to detect pathogenic/likely pathogenic mutations in LDLR, APOB, PCSK9, LDLRAP1 and 22 other lipid-related genes. In those with mutations, cascade screening was performed. Lipid and gene profiles, by capillary sequencing, were tested in family members (FM). Statistical analysis was performed using STATA.

Out of 610 probands, there were 175 and 17 LDLR and APOB mutations, respectively. One hundred and ninety-three FM were screened through 192 probands, with 100 of them being mutation-positive (M+). Highest documented total cholesterol(TC) and LDL-C of probands versus M+:[7.9(7.0 – 9.5) vs 6.6(5.8-7.7),p<0.0001]mmol/l and [6.2(5.4-7.6) vs 4.9 (4.1-5.9),p<0.0001]mmol/l. Of the FM who were M+, 59 (59%) were previously undiagnosed and in those previously diagnosed, their LDL-C was (5.1±0.3)mmol/l on recruitment.

The local cascade screening in FH yielded 0.5new case per proband. FM (M+) had lower TC and LDL-C than probands and were mostly under-treated.