Résumé :
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Communication n° 54. Introduction : Decrease mitochondrial thymidine kinase (TK2) activity is associated with mitochondria DNA (mt DNA) depletion syndromes (MDS) and respiratory chain dysfuntion. Mutations in TK2 gene have been associated with isolated, severe and progressive myopathy in the first years of life. The present study shows a novel mutation in TK2 gene in a child with severe myopathy and mt DNA depletion. Patient and method : A 5 years old boy, whose parents were not consanguineous had normal early development until 2 and a half years. At this stage he fell frequently down showing difficulties in walking and getting up from the floor. Over the next 2 years he developed generalised weakness and wasting but extra ocular muscles movement were sparing and no ptosis were noticed. Sensorial, cerebellar and cognitive functions were preserved. Deep tendon reflexes were diminished. Maximum level of CK was 540 IU/L, (normal values up 190 IU/L). Mild lactacidemia was observed. Brainstaim auditory evocated potentials were compatible with hypoacusia. Motor and sensory nerve conduction were normal, needle EMG showed myogenic pattern. Muscle biopsy : It showed deeply muscle atrophy with fat vacuoles in them. COX negative and RRF morphology were observed. Biochemistry : Respiratory chain complexes activities in muscle were all decreased. Genetic studies: Sequence analysis of the coding region of the TK2 gene revealed two heterozygous mutations, in exon 8 a trinucleotide deletion, abolishing lysine at codon 171 and an insercion nucleotide adenine in exon 2. Deeply mtDNA depletion ( more than 90% in muscle), was detected. Conclusions . Severe and progressive muscle atrophy may lead to search for evidence of mitochondrial dysfunction and should alert the clinician to the possible diagnosis of TK2 deficiency. Our findings extend the list of TK2 mutations associated with myopathic form of MDS.
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