Transient neonatal diabetes - Widening the understanding of the etiopathogenesis of diabetes

Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberr ations of chromosome 6. A genotype/phenotype study was also performed. Geno typically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome ba nd 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadi c cases). Most patients were growth retarded at birth, presented at a media n age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 r elatives of the TND patients who presented with type 2 diabetes and no earl y history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in similar to 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal pr esentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in norma l pancreatic development.