Type 1 Hyperlipoproteinemia Due to Compound Heterozygous Rare Variants in GCKR

Background: Type 1 hyperlipoproteinemia (T1HLP) is a rare, autosomal recessive disorder characterized by extreme elevations in serum triglyceride (TG) levels. Despite considerable progress in identifying several causal genes for T1HLP, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1, the molecular basis of some extremely rare patients presenting with T1HLP remains obscure. Case Description: We report a 58-year-old Hispanic female who initially presented with serum TG of 4740 mg/dL at age 23 years when she was 3 weeks postpartum and was taking an oral contraceptive for 2 weeks. Over a period of 35 years, she has had recurrent episodes of extreme hypertriglyceridemia (fasting serum TG exceeding 2000 mg/dL), which responded to a reduction of dietary fat, fibrates, and fish oil therapy. Sanger sequencing of the known T1HLP genes in this patient did not reveal any disease-causing mutations. Whole-exome sequencing revealed compound heterozygous rare variants (p.Val103Met and p.Arg540Gln) in the glucokinase regulat...