A Multisystem Mitochondrial Disease Caused by a Novel MT-TL1 mtDNA Variant: A Case Report

Abstract

Background: Mitochondrial tRNA (MTT) genes are hotspot for mitochondrial DNA mutation and are responsible of half mitochondrial disease. MTT mutations are associated with a broad spectrum of phenotype often with complex multisystem involvement and complex genotype-phenotype correlations. MT-TL1 mutations, among which the m.3243A>G mutation is the most frequent, are associated with myopathy, maternal inherited diabetes and deafness, MELAS, cardiomyopathy, and focal segmental glomerulosclerosis.

Case study: Here we report the case of an Italian 49-years old female presenting with encephalomyopathy, chronic proteinuric kidney disease and a new heteroplasmic m.3274_3275delAC MT-TL1 gene mutation.

Conclusions: Our case demonstrates a systemic mitochondrial disease caused by the heteroplasmic m.3274_3275delAC MT-TL1 gene mutation, not yet described in the literature. A mitochondrial disease should be suspected in case of complex multisystem phenotypes, including steroid-resistant nephrotic syndrome with multisystemic involvement.

Keywords: glomerulosclerosis; kidney disease; mitochondrial diseases; mitochondrial myopathies; mtDNA.

Fig. 1

Brain MRI: a. Axial T2, showing global cerebral atrophy with ex-vacuo lateral ventricles dilatation; b. Sagittal T2, cerebellar atrophy; c. MR spectroscopy: the white asterisk (*) marks the lactate peak; d. axial T1 and e. susceptibility-weighted angiography (SWAN): mild bipallidal calcifications.

Fig. 2

Muscle biopsy reveals mild proliferation of mitochondria (a), COX negative fibers (b) and (c) one ragged blue fiber.