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Eur J Hum Genet. 2014 Oct;22(10):1229-32. doi: 10.1038/ejhg.2014.8. Epub 2014 Feb 19.

A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia.

Author information

1
1] Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA [2] The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
2
1] Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA [2] Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA [3] The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
3
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
4
Department of Cardiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
5
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
6
Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.

Abstract

The constellation of clinico-pathological and laboratory findings including massive hepatomegaly, steatosis, and marked hypertriglyceridemia in infancy is extremely rare. We describe a child who is presented with the above findings, and despite extensive diagnostic testing no cause could be identified. Whole exome sequencing was performed on the patient and parents' DNA. Mutations in GPD1 encoding glycerol-3-phosphate dehydrogenase that catalyzes the reversible redox reaction of dihydroxyacetone phosphate and NADH to glycerol-3-phosphate (G3P) and NAD(+) were identified. The proband inherited a GPD1 deletion from the father determined using copy number analysis and a missense change p.(R229Q) from the mother. GPD1 protein was absent in the patient's liver biopsy on western blot. Low normal activity of carnitine palmitoyl transferases, CPT1 and CPT2, was present in the patient's skin fibroblasts, without mutations in genes encoding for these proteins. This is the first report of compound heterozygous mutations in GPD1 associated with a lack of GPD1 protein and reduction in CPT1 and CPT2 activity.

PMID:
24549054
PMCID:
PMC4169545
DOI:
10.1038/ejhg.2014.8
[Indexed for MEDLINE]
Free PMC Article

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