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Deletion of GPIHBP1 causing severe chylomicronemia
Jonathan J Rios1, Savitha Shastry, Juan Jasso
1Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Journal of Inherited Metabolic Disease
|October 20, 2011
Summary
Complete deficiency of glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) causes severe hypertriglyceridemia. This study identifies a novel deletion causing GPIHBP1 deficiency in neonates, impacting triglyceride metabolism.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Lipoprotein lipase (LPL) hydrolyzes triglycerides, releasing fatty acids for tissue utilization.
- Glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) transports LPL to capillary endothelium.
- Mutations in LPL, apolipoprotein C2, or GPIHBP1 lead to severe hypertriglyceridemia.
Observation:
- A neonate presented with severe chylomicronemia.
- Genomic analysis revealed homozygosity for a 17.5-kb deletion encompassing the GPIHBP1 gene.
- Affected family members also exhibited hypertriglyceridemia and carried the GPIHBP1 deletion.
Findings:
- Complete deficiency of GPIHBP1 was confirmed in the affected individuals.
- Intravenous heparin administration did not increase circulating LPL or decrease triglyceride levels in GPIHBP1-deficient patients, unlike in controls.
- This indicates a critical role for GPIHBP1 in heparin-releasable LPL activity.
Implications:
- This study describes the first neonate with complete GPIHBP1 deficiency due to a homozygous deletion.
- Submicroscopic deletions, identified via advanced copy-number analysis, may play a more significant role in Mendelian disorders.
- Understanding GPIHBP1's function is crucial for managing hypertriglyceridemia and related metabolic disorders.
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