[P1-157] Myopathic Mitochondrial DNA Depletion Syndromes in two Chinese patients with novel TK2 mutations presenting with developmental regression in late infancy
Mitochondrial DNA depletion syndromes(MDS) are a clinically and molecularly heterogeneous group of diseases. The myopathic form of mitochondrial DNA depletion syndromes (OMIM #609560) is mainly caused by mutations in the TK2 gene, which encodes the thymidine kinase 2, the first and rate limiting step enzyme in the phosphorylation of pyrimidine nucleosides. Here we report two patients of MDS who presented with developmental regression at the late infancy, one of which appeared to be a little fat with stiff and swell fingers and toes. On examination, the patients had weakness in proximal muscles of all four limbs. Skeletal muscle biopsy showed ragged red fiber and COX enzyme activity deficiency. Molecular analysis revealed compound heterozygous variants in the Tk2 gene for each patient, including 3 novel pathogenic variants: c.659T>C (p.L220P), c. 497A>T (p.D166V) and c.144_145del (p.E48fs). Further structural analysis revealed the probable pathogenic mechanism for these novel missense pathogenic variants. Our study further expanded the clinical and molecular spectrum of this disease.