Reply to: mitochondrial diabetes in Germany and Austria

Excerpt

We respond to the letter to the editor by J Finsterer and M Frank on our original article “Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry” [5]. In their letter, Finsterer and Frank comment that they do not agree with the statement that diabetes is a rare phenotypic manifestation in primary mitochondrial disorders [3]. While we appreciate the interest in our work, we would like to highlight that we never provided such a statement in our publication. While within the group of mitochondrial diseases, diabetes mellitus is indeed a common diagnosis [5, 7]; this does not apply vice versa. Within the group of juvenile diabetes patients, diabetes of mitochondrial origin (DMO), e.g., MIDD (OMIM # 520000) or Kearns Sayre (OMIM # 530000) syndrome, still affects only a very small subgroup of about 0.8 % of diabetes cases in Europe [4]. The exact prevalence remains unknown to date. Current prevalence estimates are generated from genetic screening in preselected diabetes populations and cannot be transferred to younger populations with a different genetic background. Moreover, combined diagnosis of diabetes and a mitochondrial mutation does not necessarily make it a diabetes of mitochondrial origin. In clinical reality, few cases in our cohort became apparent, while more cases may have a pathogenic mutation. Finsterer and Frank correctly point out that disease severity does not only depend on heteroplasmy rates but also on secondary mutations, oxidative stress, and penetrance [2]. This topic was clearly beyond the scope of our report. …