Prevalence and clinical characteristics of maternally inherited diabetes and deafness caused by the mt3243A > G mutation in young adult diabetic subjects in Sri Lanka

Diabet Med. 2008 Mar;25(3):370-4. doi: 10.1111/j.1464-5491.2007.02377.x. Epub 2008 Feb 13.

Abstract

Aims: The maternally inherited mt3243A > G mutation is associated with a variable clinical phenotype including diabetes and deafness (MIDD). We aimed to determine the prevalence and clinical characteristics of MIDD in a large South Asian cohort of young adult-onset diabetic patients from Sri Lanka.

Methods: DNA was available from 994 subjects (age of diagnosis 16-40 years, age at recruitment < or = 45 years). Mutation screening was performed using a QRT-PCR method on an ABI 7900HT system using sequence-specific probes. Samples with heteroplasm > or = 5.0% were considered positive.

Results: Nine (four males) mutation-positive subjects were identified (prevalence 0.9%). They were diagnosed at a younger age (25.9 +/- 4.8 years vs. 31.9 +/- 5.6 years, P = 0.002) and were lean (body mass index [BMI] 18.7 +/- 2.7 kg/m(2) vs. 24.7 +/- 4.0 kg/m(2), P < 0.001) compared to NMCs. One mutation-positive subject (11.1%) had metabolic syndrome, compared to 633 (64.3%) of NMCs. Insulin therapy within 6 months of diagnosis was used in four (44.0%) carriers compared to 6.9% of NMCs (P = 0.002). Combined screening criteria of any two of maternal history of diabetes, personal history of hearing impairment and family history of hearing impairment only identified five (55%) of the carriers, with a positive predictive value of 7.4%.

Conclusions: The prevalence of mt3243A > G mutation among young adult-onset diabetic subjects from Sri Lanka was 0.9%. Our study demonstrates that a maternal family history of diabetes and either a personal and/or family history of deafness only distinguish half of patients with MIDD from Sri Lankan subjects with young-onset diabetes.

MeSH terms

  • Adolescent
  • Adult
  • DNA, Mitochondrial / genetics*
  • Deafness / complications
  • Deafness / genetics*
  • Diabetes Mellitus / genetics*
  • Female
  • Humans
  • Male
  • Mutation / genetics*
  • Pedigree
  • Pregnancy
  • Sri Lanka

Substances

  • DNA, Mitochondrial