GPD1 deficiency-a rare, overlooked cause of liver disease

Abstract

Transient infantile hypertriglyceridemia is one of the diseases that should be considered in case of unexplained elevated liver enzymes, hypertriglyceridemia and hepatosteatosis. We report 2 siblings with novel homozygous variants in the GPD1 gene with transient infantile hypertriglyceridemia. Two siblings born from consanguineous marriage were referred due to hepatomegaly, elevated transaminases and fatty liver. After excluding other possible causes of fatty liver and elevated transaminase levels; whole-exome sequencing (WES) was performed on genomic DNA isolated from the peripheral blood samples of both patients. Whole exome sequencing revealed the identification of a novel homozygous variant, c.628 G > C:p.G210R, in GPD1. Our report underscores the importance of genome sequencing in diagnosing unexplained childhood fatty liver disease and/or elevated enzyme levels. In patients with transient infantile hypertriglyceridemia, investigation into novel homozygous variants in the GPD1 gene should be conducted using whole exome sequencing.

Fig. 1

A novel homozygous GPD1 mutation in two siblings with HTGTI. A Pedigree of the family, the patients are shown in black and the healthy individuals are shown in white. Where available GPD1 mutation (p.G210R) is indicated. B Familial segregation of the GPD1 mutation and its homozygous state in the patient were confirmed by Sanger sequencing. C Conservation of the p.G210 residue, highlighted in bold, across various species. (Source: NCBI HomoloGene). D Schematic representation of GPD1 mutations. The novel mutation identified in this study are indicated in bold red letters