Neema Chokshi1, Sarah D Blumenschein2, Zahid Ahmad1, Abhimanyu Garg3. 1. Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition. 2. Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390. 3. Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition. Electronic address: abhimanyu.garg@utsouthwestern.edu.
Abstract
CONTEXT: Type I hyperlipoproteinemia (T1HLP) is a rare, autosomal recessive disorder characterized by extreme hypertriglyceridemia that fails to respond to lipid-lowering agents, predisposing to frequent attacks of acute pancreatitis. Mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), lipase maturation factor 1 (LMF1), glycosyl-phosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and apolipoprotein AV (APOA5) cause T1HLP, but we lack data on phenotypic variations among the different genetic subtypes. OBJECTIVE: To study genotype-phenotype relationships among subtypes of T1HLP patients. DESIGN/INTERVENTION: Genetic screening for mutations in LPL, APOC2, GPIHBP1, LMF1, and APOA5. SETTING: Tertiary referral center. PATIENTS: Ten patients (7 female, 3 male) with chylomicronemia, serum triglyceride levels about 2000 mg/dL, and no secondary causes of hypertriglyceridemia. MAIN OUTCOME MEASURES: Genotyping and phenotypic features. RESULTS: Four patients harbored homozygous or compound heterozygous mutations in LPL, 3 had homozygous mutations in GPIHBP1, and 1 had a heterozygous APOA5 mutation. We failed to fully identify the genetic etiology in 2 cases: 1 had a heterozygous LPL mutation only and another did not have any mutations. We identified 2 interesting phenotypic features: the patient with heterozygous APOA5 mutation normalized triglyceride levels with weight loss and fish oil therapy, and all 7 female patients were anemic. CONCLUSIONS: Our data suggest the possibility of novel loci for T1HLP. We observed that heterozygous APOA5 mutation can cause T1HLP but such patients may unexpectedly respond to therapy, and females with T1HLP suffer from anemia. Further studies of larger cohorts may elucidate more phenotype-genotypes relationships among T1HLP subtypes. Published by Elsevier Inc.
CONTEXT: Type I hyperlipoproteinemia (T1HLP) is a rare, autosomal recessive disorder characterized by extreme hypertriglyceridemia that fails to respond to lipid-lowering agents, predisposing to frequent attacks of acute pancreatitis. Mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), lipase maturation factor 1 (LMF1), glycosyl-phosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and apolipoprotein AV (APOA5) cause T1HLP, but we lack data on phenotypic variations among the different genetic subtypes. OBJECTIVE: To study genotype-phenotype relationships among subtypes of T1HLP patients. DESIGN/INTERVENTION: Genetic screening for mutations in LPL, APOC2, GPIHBP1, LMF1, and APOA5. SETTING: Tertiary referral center. PATIENTS: Ten patients (7 female, 3 male) with chylomicronemia, serum triglyceride levels about 2000 mg/dL, and no secondary causes of hypertriglyceridemia. MAIN OUTCOME MEASURES: Genotyping and phenotypic features. RESULTS: Four patients harbored homozygous or compound heterozygous mutations in LPL, 3 had homozygous mutations in GPIHBP1, and 1 had a heterozygous APOA5 mutation. We failed to fully identify the genetic etiology in 2 cases: 1 had a heterozygous LPL mutation only and another did not have any mutations. We identified 2 interesting phenotypic features: the patient with heterozygous APOA5 mutation normalized triglyceride levels with weight loss and fish oil therapy, and all 7 female patients were anemic. CONCLUSIONS: Our data suggest the possibility of novel loci for T1HLP. We observed that heterozygous APOA5 mutation can cause T1HLP but such patients may unexpectedly respond to therapy, and females with T1HLP suffer from anemia. Further studies of larger cohorts may elucidate more phenotype-genotypes relationships among T1HLP subtypes. Published by Elsevier Inc.
Authors: Xuchen Hu; Geesje M Dallinga-Thie; G Kees Hovingh; Sandy Y Chang; Norma P Sandoval; Tiffany Ly P Dang; Isamu Fukamachi; Kazuya Miyashita; Katsuyuki Nakajima; Masami Murakami; Loren G Fong; Michael Ploug; Stephen G Young; Anne P Beigneux Journal: J Clin Lipidol Date: 2017-06-13 Impact factor: 4.766