Genetic spectrum of familial hypertriglyceridemia from the southeastern region of Turkey

Aim: The disorders of lipid metabolism that cause primary hypertriglyceridemia result from genetic defects in triglyceride synthesis and metabolism. Although primary causes are rare in hypertriglyceridemia, they should be considered in severe hypertriglyceridemia cases. Identified genetic mutations are LPL, APOC2, APOA5, LMF1 and GPIHBP1 mutations. Material and Methods: This descriptive cross-sectional study was conducted in Diyarbakir Children's Hospital pediatric metabolism clinic on 60 patients from 41 unrelated families who were followed and diagnosed with severe hypertriglyceridemia based on clinical presentation, neurological parameters, biochemical measurements, and molecular analysis. The LPL, APOC2, APOA5, LMF1, GPIHBP1 genes were sequenced in 60 patients. Patients with initial triglyceride levels >885mg/dL were included in the study. Patients with a secondary cause were excluded from the study. Results: Rare DNA sequence variants were identified in 49 patients (81.66%), including variants LPL (n=15), APOC2 (n=32), and APOA5 (n=2). No mutations were found in 11 patients (21%). The mean initial triglyceride level was 4322.8 +/- 4483mg/dL. Acute pancreatitis occurred in 38.33% (n=23) of the patients. The incidence of eruptive xanthoma was 28.33%, organomegaly was 23.33%, and failure to thrive was 21.66%. 69.23% of the patients with failure to thrive were patients with pancreatitis. Two different variants, c.55+6T>G and c.55+1G>C were detected in the APOC2 gene, seven different variants one of which is novel, c.557G>A, c.953A>G, c.296T>C, c.662T>C, c.1262G>A, c.644G>A and c.679G>C, were detected in the LPL gene, and two different variants one of which is novel, c.334_399dup65bp and c.16_39del24bp were detected in the APOA5 gene. Six patients were homozygous for both c.557G>A and c.953A>G variants. Discussion: The frequency of mutations in APOC2 was 50%, LPL was 25% and APOA5 was %3.33. The relatively high prevalence of APOC2 mutations in our cohort may be due to regional frequency. The development of new therapeutic options for this rare disease requires awareness and screening among these patients. These findings highlight the need for molecular analysis in patients with severe HTG. It is anticipated to guide future individualized therapeutic strategies.