Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype

Excerpt

To the Editor: Methylation defects at chromosome 6q24 are the most common cause of transient neonatal diabetes mellitus (TNDM), accounting for 70% of all cases [1, 2]. Those affected have impaired insulin secretion, as shown by a very low birthweight (median below the first centile) and a diagnosis of diabetes usually at or shortly after birth (range 0–4 weeks) [1‐3]. In most cases the diabetes remits by a median age of 13 weeks, although many will experience a relapse later in life [3]. Loss of methylation at the chromosome 6q24 locus results from one of three mechanisms: (1) paternal uniparental disomy (UPD) (approximately 40% of cases); (2) paternal duplication (approximately 32% of cases); or (3) loss of methylation without a structural chromosome defect (approximately 28% of cases) (reviewed in [2]). The TNDM critical region on chromosome 6q24 encompasses PLAGL1, a tumour-suppressor gene, and HYMAI, a non-coding RNA of unknown function [2]. The underlying mechanism(s) by which loss of methylation, and hence overexpression, of PLAGL1 and/or HYMAI cause TNDM is not known. …