Mitochondrial DNA depletion syndrome presenting with ataxia and external ophthalmoplegia: Case report

• Published in: The Egyptian journal of medical human genetics 2012-10, Vol.13 (3), p.351-357
• Main Authors: Selim, Laila, Mehaney, Dina, Hassan, Fayza, Sabry, Randa, Zeyada, Reham, Hassan, Sawsan, Eldin, Iman Gamal, Bertini, Enrico
• Format: Article
• Language: English
• Subjects: Depletion; Diseases; Eye; Eye Paralysis; Genetic aspects; Mitochondrial; Mitochondrial DNA; Mutations; Nuclear; Sequencing; الأمراض; الجوانب الوراثية
• ISSN: 1110-8630; 2090-2441
• DOI: 10.1016/j.ejmhg.2012.05.003

The mitochondrial DNA depletion syndromes are autosomal recessive disorders characterized by decreased mitochondrial DNA copy number in affected tissues. Mutations in 2 genes involved in deoxyribonucleotide metabolism, the deoxyguanosine kinase gene and the thymidine kinase 2 gene, had been related to this syndrome. This study aims to describe the clinical, histochemical, biochemical and molecular diagnosis of one Egyptian pediatric patient with the myopathic form of mitochondrial depletion syndrome. The patient presented to Cairo University Pediatric Hospital with the clinical suspicion of mitochondrial encephalomyopathy. Histochemical and biochemical studies of the respiratory chain complexes were performed on the muscle biopsy specimen from the patient. Molecular diagnosis was done by quantitative radioactive Southern blot and sequencing analysis of the whole coding regions of the TK2 gene. Histochemical staining revealed cytochrome oxidase negative fibers and increased staining for succinate dehydrogenase. The activity of complex I was not detected and complex IV activity was about 46% of age matched controls. Southern blot analysis showed reduction of the mitochondrial/nuclear DNA ratio, the degree of depletion was around 30% of aged-matched controls. Sequencing analysis of the TK2 gene revealed no sequence variation. Targeted molecular diagnosis based on the biochemical analysis of the respiratory chain enzymes makes the molecular evaluation of mitochondrial disorders much easier. Involvement of other nuclear genes rather than TK2 gene in the pathogenesis of the myopathic form of mitochondrial depletion syndrome should be considered.