Activating mutations in the gene encoding Kir6.2 alter fetal and postnatal growth and also cause neonatal diabetes

The Journal of Clinical Endocrinology and Metabolism
Annabelle S Slingerland, Andrew T Hattersley

Abstract

Birth weight is a bioassay for fetal insulin secretion because altered insulin secretion in utero alters insulin-mediated growth. Activating mutations in Kir6.2 are the major cause of neonatal diabetes and reduce insulin secretion by altering the closure of the beta-cell ATP-sensitive potassium channel in the presence of ATP. Our objective was to examine fetal and postnatal growth in patients with activating Kir6.2 mutations and identify whether this was modified by severity of mutation or maternal diabetes. We used sd scores (SDS) for birth and postnatal growth in an international series of patients (n = 49) with Kir6.2 mutations and related this to their clinical phenotype. Birth weight was greatly reduced [-1.73 (-3.68 to 1.41), median (range) SDS], but there was postnatal catch-up because present weight was normal [-0.37 (-4.37 to 2.34) SDS]. Catch-up growth for height and weight was not seen until insulin treatment was started. Birth weight was not influenced by severity of postnatal phenotype but was increased by maternal diabetes -0.12 vs. -1.81 SDS (P = 0.037). Patients with the severe neurological developmental delay, epilepsy, and neonatal diabetes syndrome did not catch up (present weight -2.2 vs. -0.24 SDS (P = 0.00...Continue Reading

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