Identification of GCK-maturity-onset diabetes of the young in cases of neonatal hyperglycemia: A case series and review of clinical features

Abstract

Heterozygous mutations in GCK result in a persistent, mildly raised glucose from birth, but it is usually diagnosed in adulthood as maturity-onset diabetes of the young (MODY), where hyperglycemia is often an incidental finding. The hyperglycemia of GCK-MODY is benign and does not require treatment, but is important to be aware of, particularly in females where it has implications for managing pregnancy. We present three cases of neonatal hyperglycemia resulting from a heterozygous mutation in GCK, illustrating its clinical presentation and evolution in early life. In summary, as with adults, neonatal hyperglycemia is an incidental finding, does not require treatment and has no adverse consequences for health. Neonates and their parents should be referred for genetic testing to confirm the diagnosis, avoid a label of diabetes and enable pregnancy counseling for females found to be affected.

Keywords: GCK-MODY; glucokinase; hyperglycemia; monogenic diabetes of the young; neonatal diabetes.

Figure 1

Partial pedigrees for cases of GCK-MODY diagnosed where hyperglycemia was first identified in the neonatal period. Filled symbols represent individuals with a genetic diagnosis of GCK-MODY, genotypes are provided under the symbols. The clinical diagnosis is provided under the symbols for individuals affected by diabetes (for the father of Case 1, the affected phenotype is assumed based on genotype). GDM = Gestational Diabetes Mellitus. T2D = Type 2 diabetes. An arrow points to the proband in each family.