Mitochondrial Myopathy Associated with Thymidine Kinase-2 Enzyme Deficiency in a Child of the First Year of Life: Case Report

Background. Mitochondrial myopathy caused by mutations in the gene encoding the mitochondrial enzyme thymidine kinase-2, located on chromosome 16 at locus 16q21 (hereinafter TK2-associated mitochondrial myopathy, OMIM: #609560), is a rare autosomal recessive genetic pathology characterized by impaired replication of mitochondrial deoxyribonucleic acid (mtDNA) with the development of the range of clinical manifestations, with the leading myopathic syndrome. Early diagnosis of the disease is important because there is a pathogenetic treatment in the form of the use of specialized foods containing deoxynucleosides.

Case report. The article presents the clinical features of the infantile form of TK2-associated mitochondrial myopathy in a 7.5-month-old girl. This girl M. is being observed at the Children’s Municipal Clinical Hospital № 1 in Nizhny Novgorod. The child was born from the fourth pregnancy and the third home birth. The girl was not observed by medical specialists for up to 2 months. The girl’s psychomotor development corresponded to age standards up to the age of 5 months. The disease debuted at 5 months of age with breastfeeding disorders, weight loss, muscle weakness, and loss of age-related skills. The patient was hospitalized at the age of 7.5 months in a severe condition: adynamia, areflexia, atony, ophthalmoparesis, partial ptosis, clinic of bulbar and pseudobulbar syndromes, hepatosplenomegaly, no psychomotor skills. The examination revealed syndromes such as severe cytolysis and rhabdomyolysis, transient hyperlactatemia, cardiomyopathy, and signs of cerebral cortex atrophy. The diagnosis of TK2-associated mitochondrial myopathy was confirmed by a molecular genetic study. Two pathogenic mutations in the compound heterozygous state were identified in exons 2 and 6 of the TK2 gene (c.144_145delGA, p.(Lys50IlefsTer99) and c.416C>T, p.(Ala139Val), respectively) associated with this disease. The mutations were validated using Sanger “trio” sequencing. The child was prescribed a specialized diet with a high content of deoxynucleosides (thymidine, deoxycytidine) at the age of 8 months, against which background the condition stabilization was noted.

Conclusion. The delayed disease diagnosis due to the late parents’ appeal for medical help from the moment of the disease onset with the belated appointment of pathogenetic therapy as the result, makes this clinical case special. The patient is prescribed lifelong use of a specialized diet. Due to the high probability of developing respiratory disorders the prognosis for this disease is doubtful. Pediatricians need to be vigilant in early detection of orphan pathology terms in the presence of “floppy infant syndrome“.

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