A Rare Case of Glycerol-3-Phosphate Dehydrogenase 1 Deficiency in a 6-Month-Old Infant

A 6-month-old male infant, the second child of healthy, non-consanguineous parents, presented with upper abdominal distension, failure to thrive, and hepatomegaly. Examination indicated a weight of 3.8 kg and length of 56 cm, along with hyperuricemia, elevated triglycerides (627 mg/dL), and liver enzyme levels. Ultrasound revealed grade II fatty liver, and a liver biopsy showed extensive steatosis and pericellular fibrosis without cirrhosis. Genetic testing identified a pathogenic splice-site mutation in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene.

The infant was placed on a low-fat, medium-chain triglyceride (MCT) diet, leading to reductions in triglycerides and liver enzymes over a six-month follow-up, although hepatomegaly persisted. Differential diagnoses for the infant's symptoms included various metabolic disorders, but the combination of fatty liver, failure to thrive, and hypertriglyceridemia, along with the absence of hypoglycemia, pointed towards GPD1 deficiency.

A lack of GPD1, which is essential for lipid metabolism, can result in hypertriglyceridemia and a fatty liver because of an excess buildup of dihydroxyacetone phosphate. This case adds to the limited number of reports of GPD1 deficiency, and it specifically highlights a novel mutation that hasn't been reported before. Hepatomegaly and hypertriglyceridemia are present in the majority of cases, although hypoglycemia is uncommon. The hypertriglyceridemia is typically transient.

While liver histology and ultrasound are helpful for diagnosis, genetic testing is less invasive and conclusive. Dietary treatment can successfully reduce triglyceride levels while majority of individuals exhibit normalisation of lipid levels and liver function without the need for liver transplantation. Routine follow-up is required for monitoring growth and liver function. In conclusion, GPD1 mutations should be considered in infants with failure to thrive, fatty liver, and hypertriglyceridemia, as the prognosis can be favorable with appropriate management.

Source: Shah A, Samanta A. Glycerol-3-Phosphate Dehydrogenase 1 Deficiency: A Rare Cause of Fatty Liver Disease in Children. Indian Pediatr.2025; 62(82). https://doi.org/10.1007/s13312-025-3365-7