title: Type 1 hyperlipoproteinemia in a child with large homozygous deletion encompassing GPIHBP1.
abstract: Type I hyperlipoproteinemia (T1HLP) usually presents with extreme hypertriglyceridemia, recurrent episodes of acute pancreatitis, lipemia retinalis, and cutaneous eruptive xanthomas. We report a unique 10-year-old male of Indian origin who presented in neonatal period with transient obstructive jaundice and xanthomas in the pancreas and kidneys. Serum triglycerides stabilized with extremely low-fat diet although he subsequently developed pancreatic atrophy. Extreme hypertriglyceridemia failed to respond to treatment with fenofibrate, fish oil, and orlistat. Whole-exome sequencing of the parents and patient was performed. Copy number variation analysis revealed a large deletion in chromosome 8 containing the entire GPIHBP1, which was confirmed by Sanger sequencing to be 54,623 bp deletion. Review of the literature revealed a slightly higher maximum triglyceride levels in those with homozygous null vs missense mutations suggesting severe disease in those with nonfunctional vs dysfunctional GPIHBP1 protein. Visceral xanthomas and pancreatic atrophy can be part of the spectrum of clinical features in patients with T1HLP. We highlight the need to perform copy number variations analysis of whole-exome sequencing data for finding disease-causing variants. There is also an urgent need to develop novel targeted therapies for patients with T1HLP.
authors: Division of Pediatric Endocrinology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
authors: Nivedita
authors: N
authors: Patni
authors: Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors: Julie
authors: J
authors: Brothers
authors: Department of Clinical Sciences, McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, USA.
authors: Chao
authors: C
authors: Xing
authors: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: abhimanyu.garg@utsouthwestern.edu.
authors: Abhimanyu
authors: A
authors: Garg
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D017353:Gene Deletion; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000235:genetics*; D008297:Male; D018110:Receptors, Lipoprotein / Q000172:deficiency* / Q000235:genetics*
chemical_list: C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein
keywords: Chylomicronemia; GPIHBP1; Type 1 hyperlipoproteinemia; Whole-exome sequencing; Xanthomas