A rare cause of infantile hypertriglyceridemia and severe liver damage: glycerol-3-phosphate dehydrogenase 1 (GPD1) deficiency

A 15-year-old adopted boy has been followed since the age of 1 year because of hepatomegaly and mild increase of liver enzymes (ALT 1.5×ULN, GGT 2×ULN). Laboratory tests revealed hypertriglyceridemia (274 mg/dl) with normocholesterolemia (166 mg/dl). He has always had a normal growth. Investigations included amino acid profile, urine organic acids, glycogen storage disease, Wilson and acid lipase deficiency. Liver ultrasound highlighted diffuse echogenicity. Liver biopsy showed cirrhosis and micro and macrovesicular steatosis compatible with metabolic causes. In the following years transaminases and GGT persisted elevated (ALT up to 3×ULN, GGT up to 9×ULN) with a progressive increase of total cholesterol and triglycerides until values of 315 mg/ dl and 1017 mg/dl respectively. Clinical examination revealed hard hepatomegaly while no xanthomas were present. Serial abdominal ultrasounds confirmed hepatomegaly with left lobe hypertrophy and increased echogenicity. No signs of portal hypertension were recorded. The last elastography value was compatible with fibrosis (11.5 kPa). Echocardiogram and supra-aortic trunks ultrasound tested normal. Next Generation Sequencing for metabolic and genetic liver disease was conducted with the identification of a homozygous mutation (c.895G>A) on GPD1 gene. GPD1 mutation interferes with dihydroxyacetone phosphate and NADH reduction to glycerol-3-phospate and NAD+ causing a defect in the glucose and lipid pathways. It is associated with hepatomegaly, hypertransaminasemia, hypertriglyceridemia and hepatic steatosis. Diagnosis confirmation requires molecular analysis. Due to the small number of patients reported and their young age, there are very few data about prognosis. Hypertriglyceridemia could decrease over time but fatty liver may evolved to hepatic fibrosis.