A Case Report Of P.Arg1138Ter Tuberous Sclerosis Complex Treated With Everolimus And Literature Review

Objective:To report a case of p.Arg1138Ter tuberous sclerosis complex treated with everolimus and literature review.Methods:The TSC1 and TSC2 gene sequences were detected with 5ml peripheral venous blood of the patient.The results were compared with the NCBI database to find the mutation site?detected by Shanghai Tongshu Biotechnology Co,Ltd.?.With the clinical features of facial fibroangiomas,an ungula fibroma,renal angiomyolipomas,cortical dysplasias,and subependymal nodules,the patient can be clinically diagnosed as tuberous sclerosis according to the 2012 TSC diagnostic criteria.The patients received everolimus for 20 weeks,the dose and days were 10mg/d for 44 days,5 mg/d for 98 days,and the average dose was 6.55 mg/d.The clinical data of the patient before and after treatment with everolimus involving symptoms,signs,imaging performances,blood testing results,adverse reactions in the therapy process were recorded and to analyse the treatment effects.Results:It's founded that the mutation site is NM₀00548.4?TSC2?:c.3412C>T?p.Arg1138Ter?with the peripheral blood DNA of the patient,which is a nonsense mutation in the 29th exon of TSC2 gene.the nucleotide change c.3412C>T,amino acid change p.Arg1138Ter.After everolimus treatment for 6 weeks,the maximum diameter of the left kidney cross section decreased by 10.7%compared with the baseline,the right was 18.7%.After 20 weeks of treatment,the maximum diameter of the left kidney cross section decreased by 13.1%compared with the baseline,and the right was 23.5%.After 20 weeks of treatment,the patient's facial angiofibromas were softer and flatter than before,although the area did not change significantly,and overall improvement.There was no significant change about the ungual fibromas.During the treatment,no rebleeding of the kidney occurred,however the patient had a urinary tract infection,which was improved after treatment with antibiotics,etc.Oral ulcer appeared once,about 5 mm in size,and improved after 1 week.After taking everolimus,the absolute value of lymphocytes decreased in the later treatment,reaching the lower limit of normal value at the20th week?0.93×10⁹/L?,and no abnormalities were found in other indicators.In the blood biochemical routine examination,there was no obvious increase in fasting blood glucose,elevated AST and ALT,elevated creatinine,and decreased blood potassium and albumin.Conclusion:The patient was founded with the TSC2 gene nonsense mutation in peripheral blood samples:NM₀00548.4?TSC2?:c.3412C>T?p.Arg1138Ter?,and with the sign of facial fibroangiomas,ungula fibroma,renal angiomyolipomas,brain manifestations of cortical dysplasias and subependymal nodules.According to the diagnostic criteria of the 2012 TSC international consensus,it's can be diagnosed with tuberous sclerosis at the genetic and clinical levels.After everolimus treatment for 20 weeks?average dose 6.55 mg/d?,the volume of both kidney tumors was significantly reduced,facial vascular fibroma was improved overall,and no serious adverse reactions occurred.