Transient Infantile Hypertriglyceridemia (HTGT1; OMIM #614480) is a rare autosomal recessive disorder, which manifests in early infancy with transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis. The inherited disorder, only recently recognized and described in a total of 11 individuals to date, has been associated with mutations in the GPD1 gene, which encodes glycerol-3-phosphate dehydrogenase 1. Of note, knockout mice lacking both the mitochondrial and cytosolic GPD isoforms died within one week of life, showing fetal ketotic hypoglycemia.
We report of a 10 months-old male patient, born to highly consanguineous parents of Arab-Muslim descent, who presented with hepatomegaly, elevated liver enzymes, hypertriglyceridemia and recurrent hypoglycemic episodes. While the initial working diagnosis was that of glycogen storage disease, an extensive evaluation had also revealed evidence of fatty liver. Subsequently, whole exome sequencing was pursued and revealed the patient to harbor a novel deleterious mutation in the GPD1 gene, and his parents as heterozygous carriers of the mutation. Further molecular analysis of 19 additional family members showed ten of them to be carriers as well. The use of urine glycerol levels as a biochemical marker of the disease was evaluated.
The clinical features of our patient as well as the novel mutation in the family expand the current knowledge of this rare disorder. In addition, as fasting hypoglycemia is a newly described feature of the disease mimicking glycogen storage disease, recognition of this entity by clinicians and consideration of GPD1 mutations in appropriate clinical settings are warranted.
