Type 1 hyperlipoproteinemia in a child with large homozygous deletion encompassing GPIHBP1

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• 作者：Nivedita Patni ; MD^a ; Julie Brothers ; MD^b ; Chao Xing ; PhD^c ; Abhimanyu Garg ; MD^d ; ^{abhimanyu.garg@utsouthwestern.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Type 1 hyperlipoproteinemia ; GPIHBP1 ; Xanthomas ; Chylomicronemia ; Whole-exome sequencing
• 刊名：Journal of Clinical Lipidology
• 出版年：2016
• 出版时间：July-August 2016
• 年：2016
• 卷：10
• 期：4
• 页码：1035-1039.e2
• 全文大小：595 K

文摘

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.