Myopathy mtDNA depletion related TK2 (TK2-related mitochondrial DNA depletion syndrome, myopathic form) - Gen TK2.

Myopathy mtDNA depletion related TK2 (TK2 - MDS) is an inherited disease, signs and symptoms usually begin in early childhood. In general, development is normal, but as muscle weakness progresses, the affected people lose motor skills, develop progressive external ophthalmoplegia, hepatomegaly, seizures and sensorineural deafness. As the disease worsens, breathing muscles weaken. Respiratory failure is the most frequent cause of death, which may occur in childhood. In rare cases, the disorder progresses slowly and affected individuals survive until adolescence or adulthood.

This process is due to mutations in the TK2 gene, located on the long arm of chromosome 16 (16q22 - q23.1). This gene encodes thymidine kinase 2 enzyme found within mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, regulation of cell growth, cell division and cell death. Thymidine kinase 2 enzyme is involved in the production and maintenance of mitochondrial DNA (mtDNA), playing a role in recycling nucleotides so that errors in the sequence of mtDNA can be repaired and new mtDNA molecules occur.

Have identified more than 30 mutations in the gene TK2 cause myopathy mtDNA depletion related TK2. About two - thirds of the amino acid mutations change in thymidine kinase 2. All mutations lead to a decrease in enzymatic activity, damaging recycling nucleotide mitochondrial DNA. The scarcity of nucleotide available for repair and production of molecules mitochondrial DNA leads to a reduction in the amount of mitochondrial DNA, which alters mitochondrial function. Further depletion of mtDNA tends to cause more severe signs and symptoms. Muscle cells of people with TK2 - MDS have very low amounts of mtDNA, ranging from 5 to 30 percent of normal. Other tissues can have 60 percent of normal amounts of mtDNA.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with myopathy mtDNA depletion related TK2 by the complete PCR amplification of the exons of the gene TK2 and its subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).