Introduction: HyperinsulinismHyperammonemia (HI/HA) syndrome is a rare autosomal disease characterized by episodes of hypoglycemia related to consumption of high-protein containing foods or fasting with associated hyperammonemia secondary to an activating mutation in the GLUD1 gene. It often remains unrecognized until later in childhood because symptomatic episodes can be misinterpreted as epilepsy if patterns of hypoglycemia with fasting and protein-rich meals are not identified.
Case: The patient is a male infant born at 37 weeks to a 25 year old G6P2 mother, who presented to the ED at 9 months of life with seizure-like activity in the setting of hypoglycemia. His past medical history is pertinent for failure to thrive. Evaluation in the OSH ED noted POC glucose 33 mg/dl and otherwise clinically stable. His blood sugar increased to 53 mg/dl after administration of apple juice and to 81 mg/dl with IV D10 water at 25 ml/h. Patient transferred to our PICU where he was found well appearing with a glucose of 59 mg/dl. Stable vital signs on admission. He was admitted with IV dextrose to keep blood sugar greater than 50 mg/dl, which was eventually discontinued. Patient was placed NPO to induce hypoglycemia. Patient maintained BG greater than 50 mg/dl for ~10 h. Patient was fed a protein rich meal, two hours after which he became hypoglycemic to 40s. Critical sample drawn when POC glucose measured at 42 mg/dl, with verified serum glucose of 31 mg/dl, insulin 5.6 uIU/ml, negative ketones, cortisol 1.8 μg/dl. On next episode of hypoglycemia, cortisol was found to be 12.6 μg/dl, ACTH 48 pg/ml and ammonia 178 μg/DL (high). Patient restricted to formula feeds, with stable glucoses. Glucose sensor placed with meal times recorded, which noted hypoglycemia with high protein content foods (milk, chicken). Genetic testing heterozygous in the GLUD1 gene for variant designated c.965>A (p.Arg322His), pathogenic for the HI/HA syndrome. Patient was started on Diazoxide 15mg PO TID (5.2 mg/kg per day) with improvement of hypoglycemic episodes.
Conclusion: HI/HA syndrome should be considered in patients with unexplained hypoglycemia, particularly if associated with hyperammonemia outside of the newborn period. A thorough clinical history, including the timing of hypoglycemia in relationship to meals and the type of foods consumed by the patient, is important in defining a pattern for hypoglycemic episodes and diagnosing more rare causes of hypoglycemia.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology