Dysferlinopathy是指一组异质性的常染色体隐性遗传疾病,会影响称为dysferlin的骨骼肌蛋白。这些突变与2B型肢带肌营养不良有关,Miyoshi肌病,无症状的高CK血症,并伴有胫骨前发病的远端肌病。
一名16岁女性出现肌痛,在她第二次接种BNT162b2mRNA(辉瑞)疫苗一周后,虚弱和深色尿液。初始血清肌酸激酶(CK)测量为153,000IU/L,最终上升趋势超过200,000IU/L。然而,稳定的肾功能排除了血液透析,允许在静脉(IV)水合和碱性利尿10天后出院。就在本次演讲前两年,患者因A组链球菌性咽炎感染并发横纹肌溶解症住院.她表现出疲劳,下肢无力,和深色少尿,CK测量984,800IU/L尝试进行静脉水化,但在她的24天住院期间最终需要进行血液透析。她的发作被认为是特发性的,当时没有进行进一步的检查。在病人目前住院期间,她在11岁时首次接种四价Gardasil疫苗后报告了类似的症状(肌痛和虚弱)。当时不需要住院治疗。现在开始全面的检查,同时患者正在接受治疗,怀疑她的第二或第三不劳累,非创伤性横纹肌溶解症.风湿病,新陈代谢,传染性,内分泌检查均无异常。患者最终进行了全外显子组测序,揭示了DYSF基因中的杂合致病变体(DYSFc.26431G>A)编码dysferlin。到目前为止,没有发生临床上明显的后遗症。
虽然有报道称有症状的杂合子携带者患有异常铁病,据我们所知,没有人与免疫原性刺激后复发性横纹肌溶解症相关。这个独特的案例演示强调了多学科护理团队的重要性,现代全外显子组基因测序的效用,以及平衡疫苗风险与收益的未来挑战。
Dysferlinopathy refers to a heterogenous group of autosomal recessive disorders that affect a skeletal muscle protein called dysferlin. These mutations are associated with limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, asymptomatic hyperCKemia, and distal myopathy with anterior tibial onset.
A 16 year old female presented with myalgia, weakness and dark urine one week after her second BNT162b2 mRNA (Pfizer) vaccine. Initial serum creatine kinase (CK) was measured at 153,000 IU/L, eventually up-trending to over 200,000 IU/L. However, stable renal function precluded hemodialysis allowing discharge after 10 days of intravenous (IV) hydration and alkaline diuresis. Just two years prior to the current presentation, the patient was hospitalized following Group A Streptococcal pharyngitis infection complicated by rhabdomyolysis. She presented with fatigue, lower extremity weakness, and dark oliguria with CK measuring 984,800 IU/L. IV hydration was attempted however hemodialysis was ultimately required throughout her 24-day hospital stay. Her episode was presumed to be idiopathic and no further work-up was performed at that time. During the patient\'s current hospitalization, she reported similar symptomology (myalgias and weakness) following her first quadrivalent Gardasil vaccine at age 11. No hospitalization was required at that time. A comprehensive workup was now initiated while the patient was being treated for her suspected second or third non-exertional, non-traumatic rhabdomyolysis. Rheumatologic, metabolic, infectious, and endocrinologic workup were all unremarkable. Patient eventually had whole exome sequencing performed which revealed a heterozygous pathogenic variant in the DYSF gene (DYSF c.2643 + 1G > A) encoding dysferlin. No clinically significant sequelae occurred thus far.
While there have been reports of symptomatic heterozygote carriers of dysferlinopathies, to our knowledge none have been associated with recurrent rhabdomyolysis after immunogenic stimuli. This unique case presentation highlights the importance of a multi-disciplinary care team, the utility of modern whole-exome gene sequencing, and the future challenges of balancing vaccine risk vs benefit.