Endocrine Abstracts

JOINT2097

Introduction: Transient Infantile Hypertriglyceridemia (HTGTI) is a rare autosomal recessive disorder caused by GPD1 mutations. It is, characterized by transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, and hepatic steatosis. Its pathophysiology and long-term metabolic consequences remain poorly understood, with only 31 genetically confirmed cases reported worldwide.

Case Presentation: The patient was born at term and delivered by cesarean section due to abruptio placenta. He presented at the age of 5 months with acute vomiting following a flu-like illness. Laboratory tests revealed elevated liver enzymes, prompting further investigation despite symptom resolution. Follow-up biochemical tests consistently showed hypertriglyceridemia and elevated liver enzymes. Abdominal ultrasound initially revealed hepatosplenomegaly with abnormal liver echotexture. A follow-up ultrasound demonstrated hepatomegaly with increased parenchymal echogenicity, suggestive of parenchymal disease with fatty changes. Genetic testing (WES) identified a homozygous likely pathogenic GPD1 variant, confirming autosomal recessive HTGTI with both parents being carriers. In the family history a 6-year-old cousin had presented at 4 months with vomiting and bronchiolitis. During hospitalization, abnormal liver function tests and hepatomegaly were noted, though jaundice was absent. Investigation showed dyslipidemia and transaminitis. Initial genetic testing was inconclusive. However, a liver biopsy showed marked steatosis and fibrosis, including porto-portal bridging. whole exome sequencing identified a GPD1 variant of uncertain significance (VUS), later reclassified as pathogenic. The biopsy showed no features of glycogen storage or metabolic disease, emphasizing the need for genetic, biochemical, and clinical correlation.

Management and Follow-Up: Management included a low-fat diet restricting long-chain triglycerides with medium-chain fatty acid supplementation. Regular monitoring of growth, development, and triglyceride levels was essential. Genetic counseling was provided to discuss the 25% recurrence risk in future pregnancies.

Conclusion: This is the first case report of HTGTI from the state of Qatar. The mechanism/s of the transient hypertriglyceridemia remains unclear and the long-term implications are also unknown. The power of WES helped with the genetic diagnosis and in terms of dietary management. Further research is needed to define its long-term metabolic consequences and optimize treatment strategies.