ESPE Abstracts (2019) 92 P3-281

New Autosomal Dominant Mutation in Glucokinase Gene Causing Congenital Hyperinsulinism Diagnosed in Adulthood

Ilana Zalmon-Koren1, Amir Peleg2, Lena Sagi-Dain2, Amalia Harari-Shaham2, Gal Larom2, Iulia Pouker3, Ben Glaser4


1Pediatric Endocrinology Clinic, Carmel Medical Center, Haifa, Israel. 2Human Genetic Institute, Carmel Medical Center, Haifa, Israel. 3Endocrinology Clinic, Lin Medical Center, Haifa, Israel. 4Endocrinology and Metabolism Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel


Introduction: Autosomal dominant congenital hyperinsulinism (CH) is characterized by congenital hypoglycemia due to mutations in any of several genes including the glucokinase (GCK) gene. It is a rare disease with variable clinical symptoms mostly treated medically but in some cases requiring surgical intervention.

Aim: We describe herein the clinical presentation and the genetic diagnosis of CH in two generations of an Israeli family.

Methods/Patients: The proband was a 25 years old male who presented with hypoglycemia (glucose 40 mg/dl normal range 70-100). He felt hypoglycemic symptoms from early age but was never treated medically. He served in the army as a combat soldier at the field unit. His mother and his brother were found to be hypoglycemic but were never treated medically. His other brother was normoglycemic.

Results: DNA sequencing of GCK gene identified a novel heterozygous missense mutation (p.(Lys459Asn), c.1377G>C) in exon 10 in the proband, his mother but not in his normoglycemic brother. Continuous glucose monitoring revealed asymptomatic low glucose levels down to 40 mg/dl (normal range 70-100) during day and night.

Conclusion: CH characterized by hypoglycemia due to a mutation in the GCK gene was diagnosed in two generations of an Israeli family. The congenital condition was not treated by medications. The mutation does not cause an unregulated insulin secretion, but highly regulated insulin secretion with a below normal basal glucose level. It is the mirror picture of the CGK mutations causing MODY 2 (maturity onset diabetes of the young). Therefore the patients do not reach life endangering situations and may be not treated medically.Obtaining a detailed personal and family medical history and, when appropriate, performing targeted genetic testing, is critical to correctly diagnose hyperinsulinemic hypoglycemia. Identifying the genetic etiology has important implications regarding medical therapy and follow-up.

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