ABSTRACT
Objective To study the clinical characteristics,muscle pathological features,diagnosis and prognosis of TK2-related mitochondrial DNA depletion syndrome(MDS).Methods Clinical and laboratory data of 2 cases of TK2-related myopathic MDS were reported.And data of previously reported 58 TK2-related MDS cases were reviewed.Results Total 60 patients consisted of 35 male and 25 female.The age of onset ranged from the birth to the age of 74 years old,and 54 of the patients were attacked at the age younger than 3 years old.Muscle weakness and hypotonia were detected in all patients,with 40 patients(including the newly diagnosed 2 cases) manifested as pure myopathic form,and 20 patients with other multiple organs involvement.Serum creatine kinase was mildly increased (211-6 500 IU/L) in 53 patients.Elevated serum lactic acid level (2.3-12.0 mmol/L)was observed in 24 patients.Muscle biopsy was available from 55 patients,and ragged red fibers and/or cytochrome C oxidase (COX)-negative fibers were detected in 48 out of them.Nine out of 11 patients received electronic microscope study showed proliferation of abnormal mitochondria.Respiratory chain enzymatic activities in skeletal muscle were reduced in 31 out of 33 patients.Marked mtDNA content reduction was observed in 36 out of 41 patients (4％-25％ of age-and tissue-matched controls).A total of 42 TK2 mutations were found in 60 patients,including 2 novel mutations c.923A ＞ G and c.619-2A ＞ T in this study.Conclusions The most common clinical manifestations of TK2-related MDS are severely,rapidly progressing myopathy with infantile or early childhood onset.As the detection rate of characteristic pathologic features in muscle is high,muscle biopsy is important for the diagnosis of TK2-related MDS.
ABSTRACT
Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.