ESPE2022 Poster Category 1 Fetal, Neonatal Endocrinology and Metabolism (30 abstracts)
Short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterized by diazoxide-responsive hyperinsulinemic hypoglycemia in the neonatal or infancy periods. These patients have severe protein (especially leucine) sensitivity. HADH mutations are recessively inherited with less than 50 patients reported so far. The mechanism behind unregulated insulin secretion in SCHAD deficiency is not understood but may involve changes in protein-protein interactions with glutamate dehydrogenase (GDH). An 11.3 year-old-boy presented to the pediatric endocrinology clinic with a recent attack of weakness, sweating and pallor with glucose stick test of 44 mg/dl, treated by sweets intake. The event occurred after having his meal and following intense physical activity. His past medical history revealed recurrent unpredictable episodes of hypoglycemia since the age of 1.8 years. The first episode was the most severe manifesting with loss of consciousness and atonia, necessitating treatment by intravenous fluids infusion at hospital, but later episodes manifested only with lethargy and the desire for sweets intake. Fasting blood glucose was always normal. A starvation test was performed by his pediatrician at the age of 9 years after a second severe attack of pallor, sweating and sleepiness with blood glucose of 35 mg/dl. Blood glucose at the end of 12-hr starvation test was 99 mg/dl, insulin was elevated 43.6 mU/ml (normal <28.4), C-peptide 8 ng/ml (normal 0.9-7.1), Cortisol 45.8 mg/dl (normal 5-25), GH 1.9 ng/ml, ammonia and lactate were both normal. Taking a detailed history revealed that his last two episodes of hypoglycemia at ages of 9 and 11 years occurred after having a high-protein meal (barbecue) followed by intense physical activity which raised the possibility of a HADH mutation, this differential diagnosis was also supported by the parents’ consanguinity. Genetic testing identified a previously reported homozygous HADH splicing mutation, c.709+39C>G. Both parents were heterozygous. Parents were advised to start treatment with diazoxide, but as the hypoglycemic episodes became rare, they decided not to treat him. The patient is currently 18 years of age and in good health. He is in his final year at school with good performance. He only reports rare mild episodes of fatigue resolving spontaneously after sweets intake. Finally, we report a mild case of hyperinsulinemic hypoglycemia due to a splicing HADH mutation that presented beyond infancy and ameliorated over long-term follow-up despite no treatment.
15 Sep 2022 - 17 Sep 2022