Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients

Docherty Louise E, Kabwama S, Lehmann A, Hawke E, Harrison L, Flanagan SE, Ellard S (Editor), Hattersley AT, Julian P Hamilton-Shield, Ennis S, Mackay DJ, Temple IK

Research output: Contribution to journalArticle (Academic Journal)

67 Citations (Scopus)

Abstract

Aims/hypothesis

6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups.

Methods

One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients.

Results

6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%.

Conclusions/interpretation

This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.
Original languageEnglish
Pages (from-to)758–762
Number of pages5
JournalDiabetologia
Volume56
Issue number4
Early online date6 Feb 2013
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Chromosome 6q24
  • DNA methylation
  • Epigenetics
  • Imprinting
  • Imprinting disorder
  • Neonatal diabetes
  • Transient neonatal diabetes mellitus

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