Cardiomyopathy and Kidney Disease in a Patient with Maternally Inherited Diabetes and Deafness Caused by the 3243A>G Mutation of Mitochondrial DNA

Abstract

Cardiomyopathy is a manifestation of mitochondrial cytopathies, but rarely constitutes the dominant feature, especially in adults. We report the case of a 59-year-old male with a personal and maternal history of diabetes and deafness, who presented with cardiomyopathy and kidney disease. We diagnosed the patient as having a mitochondrial cytopathy resulting from the 3243A>G mutation on the tRNA^Leu(UUR) gene in the mitochondrial DNA. The family history, broad spectrum of clinical manifestations and fluctuant clinical course provided clues to the diagnosis. We discuss the possible mechanisms underlying the phenotypic variability and fluctuant clinical course of mitochondrial disorders and the potential usefulness of coenzyme Q10 and L-carnitine in 3243A>G mutation patients.

Atrial Fibrillation Is Poorly Tolerated by Patients with Hypertrophic Concentric Cardiomyopathy Caused by Mitochondrial tRNALeu (UUR) Mutations

“…14,15 Typical for A3243G disorders is the wide variation in clinical manifestations, but only few case reports of CMP as a major presenting manifestation exist. [8][9][10][11][12][13] We conclude that cardiac manifestations associated to A3243G and T3258C mutations, despite the common occurrence of the former, 9,16,17 are not well known among physicians. If diagnosed early, the malignant disease course of these mitochondrial CMPs upon atrial fibrillation could be affected by prompt intervention.…”

“…7 A3243G mutation in tRNA Leu(UUR) of mtDNA has been occasionally reported to include CMP as part of the disease manifestation. [8][9][10][11][12][13] This mutation typically manifests as mitochondrial myopathy and encephalopathy 14 or as maternally inherited diabetes and deafness 15 with high populationdependent frequency: from 1:420 in Australia to ~1:5000 -1:10,000 in UK and Finland. 9,16,17 We report here the molecular genetics and presentation of mitochondrial myopathy with hypertrophic CMP in three families.…”

Therapeutic Strategies for Mitochondrial Disorders

“…6 Besides its important role in the metabolism of lipids, L-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. 7 Evidence for its effectiveness to treat mitochondrial disorders derives mainly from case reports. [7][8][9] In a randomized, placebo-controlled trial over 3 months in patients with autism spectrum disorders, application of L-carnitine (50 mg/kg/d) resulted in a significant improvement in the childhood autism rating scale, clinical global impression, and autism treatment evaluation checklist.…”

“…7 Evidence for its effectiveness to treat mitochondrial disorders derives mainly from case reports. [7][8][9] In a randomized, placebo-controlled trial over 3 months in patients with autism spectrum disorders, application of L-carnitine (50 mg/kg/d) resulted in a significant improvement in the childhood autism rating scale, clinical global impression, and autism treatment evaluation checklist. 10 There is some evidence that autism spectrum disorders are associated with mitochondrial dysfunction.…”

Keep the fire burning: Current avenues in the quest of treating mitochondrial disorders

“…Patients with respiratory chain defects often have reduced free carnitine levels (DiMauro et al, 2006). Although L-carnitine, as part of vitamin cocktails, is commonly used in patients with mitochondrial diseases evidence for its effectiveness derives mainly from case reports (Azevedo et al, 2010;Wei et al, 2009).…”