(CSEMP023) HYPERINSULINISM/HYPERAMMONEMIA (HI/HA) SYNDROME IN PREGNANCY: A CLINICAL VIGNETTE

Abstract:

Introduction: Hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant metabolic disease caused by gain of function mutations in the GLUD1 gene. Over production of mitochondrial enzyme glutamate dehydrogenase (GDH) leads to excess insulin production by pancreatic β-cells and increase in ammonia levels. The most common clinical manifestations are neonatal recurrent severe hypoglycemia and seizures leading to cerebral damage, cognitive impairment and learning disability. In adulthood, management of HI/HA is centered around minimizing hypoglycemia risk through dietary and pharmacologic interventions. Commonly used medications include diazoxide, somatostatin analogues, and calcium channel blockers. Yet, little is known about the management of HI/HA in pregnancy, and the safety of the use of these agents.

Methods: In this report, we present a case of a 26-year-old female with HI/HA and GLUD1 gene mutation. She presented for evaluation with an unplanned pregnancy at 20 weeks gestational age. The patient’s clinical history, hospitalization and treatments received during pregnancy are detailed. We review the limited literature on this topic and discuss the risks and benefits of various treatment strategies previously described.

Results: The patient was followed closely at our High risk Obstetrics clinic, with weekly monitoring of ammonia and glucose levels. Continuous glucose monitoring device was used to allow the patient to predict and manage low blood sugars. With the assistance of a dietician, the patient implemented a high carbohydrate and leucine restricted diet. She was unable to tolerate cornstarch for hypoglycemia prevention due to symptoms of severe nausea. Prior to pregnancy she was managed with diazoxide 400mg twice daily and verapamil 80 mg daily. During pregnancy, her verapamil was discontinued and diazoxide dose reduced to 200mg twice daily due to concern regarding potential teratogenic effects. An attempt to discontinue diazoxide resulted in hospitalization for severe hypoglycemia and seizure. Serial fetal ultrasounds showed normal anatomy with some symmetric growth restriction. She had a successful term delivery at 37 weeks via cesarean section.

Conclusion: HI/HA is a rare disorder that is challenging to manage in pregnancy. Optimal management involves a multidisciplinary approach that comprises optimization of dietary and pharmacologic interventions. Diazoxide has limited evidence of safety in human pregnancy but significant risks in animal studies. Octreotide is potentially an alternative option for refractory hypoglycemia, but has limited experience in pregnancy and unclear fetal risks. We recommend preconception counselling to highlight these uncertainties.