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.
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Acknowledgements
We acknowledge the financial support from the Gene Discovery Core of The Manton Center for Orphan Disease Research at Boston Children’s Hospital. Sanger sequencing was performed by the Molecular Genetics Core Facility of the IDDRC at Boston Children's Hospital supported by National Institute of Health (NIH) P30HD18655. PBA was supported by K08 AR055072 from the NIH.
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Joshi, M., Eagan, J., Desai, N. et al. A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia. Eur J Hum Genet 22, 1229–1232 (2014). https://doi.org/10.1038/ejhg.2014.8
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DOI: https://doi.org/10.1038/ejhg.2014.8
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