Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation

J Inherit Metab Dis. 2012 Nov;35(6):1059-69. doi: 10.1007/s10545-012-9465-2. Epub 2012 Mar 9.


The m.3243A>G mutation has become known as the MELAS mutation. However, many other clinical phenotypes associated with this mutation have been described,most frequently being Maternally Inherited Diabetes and Deafness (MIDD). The m.3243A>G mutation, can be detected in virtually all tissues, however heteroplasmy differs between samples. Recent reports indicate, a preference to perform mutation analysis in Urinary Epithelial Cells(UEC). To test this, and to study a correlation between the mutational load in different tissues with two mitochondrial scoring systems (NMDAS and NPMDS) we investigated 34 families carrying the m.3243A>G mutation. Heteroplasmy was determined in three non-invasively collected samples,namely leucocytes, UEC and buccal mucosa. We included 127 patients, of which 82 carried the m.3243A>G mutation.None of the children (n011) had specific complaints. In adults(n071), a median NMDAS score of 15 (IQR 10-24) was found. The most prevalent symptoms were hearing loss(68 %), gastro-intestinal problems (59 %), exercise intolerance(54 %) and glucose intolerance (52 %). Ten patients had neurologic involvement. Buccal mucosa had the best correlation with the NMDAS in all adults (r00.437, p<0.001),whereas UEC had the strongest correlation with the NMDAS in severely affected patients (r00.593, p00.002). Heteroplasmy declined significantly with increasing age in all three samples (leucocytes r0-0.705 (p<0.001), UEC r0-0.374 (p00.001), buccal mucosa r0-0.460 (p<0.001). In our cohort of 82 patients, the m.3243A>Gmutation causes a wide variety of signs and symptoms, MIDD being far more prevalent than MELAS. Looking at the characteristics of the three noninvasively available tissues for testing heteroplasmy we confirm that UEC are the preferred sample to test [corrected].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Composition
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / urine
  • Deafness / genetics*
  • Deafness / metabolism*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Heterozygote
  • Humans
  • Infant
  • MELAS Syndrome / genetics*
  • MELAS Syndrome / metabolism*
  • Male
  • Middle Aged
  • Mitochondrial Diseases
  • Netherlands
  • Phenotype
  • Point Mutation*
  • Quality of Life
  • RNA, Transfer / genetics
  • Saliva / metabolism
  • Young Adult


  • DNA, Mitochondrial
  • RNA, Transfer

Supplementary concepts

  • Noninsulin-dependent diabetes mellitus with deafness