Original Article

Journal of Inherited Metabolic Disease

, Volume 35, Issue 3, pp 531-540

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Deletion of GPIHBP1 causing severe chylomicronemia

  • Jonathan J. RiosAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center
  • , Savitha ShastryAffiliated withDivision of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center
  • , Juan JassoAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center
  • , Natalie HauserAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center
  • , Abhimanyu GargAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterDivision of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center
  • , André BensadounAffiliated withDivision of Nutritional Sciences, Cornell University
  • , Jonathan C. CohenAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterDivision of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center Email author 
  • , Helen H. HobbsAffiliated withEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical CenterHoward Hughes Medical Institute, University of Texas Southwestern Medical Center Email author 

Abstract

Lipoprotein lipase (LPL) is a hydrolase that cleaves circulating triglycerides to release fatty acids to the surrounding tissues. The enzyme is synthesized in parenchymal cells and is transported to its site of action on the capillary endothelium by glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Inactivating mutations in LPL; in its cofactor, apolipoprotein (Apo) C2; or in GPIHBP1 cause severe hypertriglyceridemia. Here we describe an individual with complete deficiency of GPIHBP1. The proband was an Asian Indian boy who had severe chylomicronemia at 2 months of age. Array-based copy-number analysis of his genomic DNA revealed homozygosity for a 17.5-kb deletion that included GPIHBP1. A 44-year-old aunt with a history of hypertriglyceridemia and pancreatitis was also homozygous for the deletion. A bolus of intravenously administered heparin caused a rapid increase in circulating LPL and decreased plasma triglyceride levels in control individuals but not in two GPIHBP1-deficient patients. Thus, short-term treatment with heparin failed to attenuate the hypertriglyceridemia in patients with GPIHBP1 deficiency. The increasing resolution of copy number microarrays and their widespread adoption for routine cytogenetic analysis is likely to reveal a greater role for submicroscopic deletions in Mendelian conditions. We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1.