8676 Hereditary Fructose Intolerance Unmasked: Report of a Pediatric Case Exploring Differential Diagnosis of Hypoglycemia and Genetic Insights
Authors: Solano Natalia , Baboun Daniela , Granados Andrea , Carrillo-Iregui Adriana 
Published: October 2024

Disclosure: N. Solano: None. D. Baboun: None. A. Granados: None. A. Carrillo-Iregui: None.

Introduction: Hereditary fructose intolerance (HFI) is an uncommon autosomal recessive metabolic disorder characterized by a deficiency of aldolase B, a crucial enzyme involved in fructose metabolism. This deficiency causes an accumulation of fructose-1-phosphate, which triggers a cascade of metabolic disturbances including hypoglycemia, lactic acidosis, and hepatic dysfunction. If left untreated, HFI can lead to severe complications, including liver failure and even death. Diagnosing HFI can be challenging due to its nonspecific clinical presentation and the absence of routine screening tests. Case presentation: A 4-year-old girl was referred from an outside hospital for hypoglycemia requiring intravenous dextrose infusion. The patient became lethargic 30 minutes after consuming a honey-based cough syrup. Upon presentation to the emergency department, her blood glucose level was 41 mg/dL. Her past medical history revealed an episode of lethargy and persistent vomiting at age 21 months, coinciding with an intussusception. A finger blood glucose test at the time was undetectable, and further evaluation revealed metabolic acidosis, elevated liver enzymes, and a normal ammonia level. Plasma amino acid, acylcarnitine, carnitine, urine acylglycine, carnitine, and urine organic acid levels were all within normal limits. Fatty acid oxidation and glycogen storage disease panels were also negative. On inquiry into her dietary habits, her parents recalled she would spit fruits out whenever tasting them, suggesting an innate aversion to fructose-rich foods. Initial comprehensive inpatient workup, including a critical sample, yielded no definitive results. She underwent a strict 24-hour inpatient fast and remained asymptomatic, with blood glucose levels above 65 mg/dL, ruling out hyperinsulinism. A broader next-generation sequencing (NGS) hypoglycemia panel was ordered, which identified a heterozygous pathogenic variant, c.178C&gt;T (p.Arg60*) maternally inherited, and a likely pathogenic variant, c.379+1G&gt;T (Splice donor) paternally inherited, in the aldolase B gene. Both confirmed the diagnosis of hereditary fructose intolerance (HFI). The family received comprehensive dietary and genetic counseling. Conclusion: HFI is an uncommon but potentially life-threatening inborn error of metabolism. Maintaining a high index of suspicion, considering a broad differential diagnosis, and obtaining a detailed dietary history, including fruit consumption, are crucial for identifying and managing HFI in infants and children with unexplained hypoglycemia. This case highlights the importance of early diagnosis and dietary intervention to prevent severe complications in patients with HFI. Additionally, it emphasizes the need for comprehensive dietary counseling and education for patients' families to ensure lifelong adherence to a fructose-restricted diet.

Presentation: 6/2/2024