肉碱缺乏所致心肌病的临床特点及治疗随访

Clinical presentation and therapeutic outcomes of carnitine deficiency-induced cardiomyopathy

目的探讨肉碱缺乏所致心肌病的临床特点以及左旋肉碱对其治疗效果。方法2010年1月到2011年12月收治的75例儿童心肌病患者，采用串联质谱检测干血滤纸片中游离肉碱和酰基肉碱的水平，对于确诊为肉碱缺乏症的患儿加用左旋肉碱治疗，剂量为150～250mg／（kg·d），所有患儿在治疗前和随访过程中进行临床评估，包括临床体检、心电图、胸x线片、心脏超声和外周血串联质谱检查。结果75例心肌病患儿中6例诊断为肉碱缺乏症，包括男性1例，女性5例，年龄为0．75～6岁，入院时外周血游离肉碱水平为（1．55±0．61）μmol／L（参考值10～60μmol／L），左室舒张末期直径（LVDd）为（5．04±0．66）cm，左室射血分数（LVEF）为（38．5±10．5）％。采用左旋肉碱治疗后早期复查（10～30d），游离肉碱升高至（30．59±15．02）μmol／L（t=4．79，P〈0．01），LVDd缩小至（4．42±0．67）cm（t=4．28，P〈0．01）；LVEF提高至（49．1±7．6）％（t=6．59，P〈0．01）。6例患儿都进行了6个月以上的随访，LVEF均恢复至正常水平；LVDd也进一步回缩，其中3例完全恢复至正常水平；所有患儿临床症状消失。治疗过程中仅1例出现间歇性腹泻，无其他并发症发生。结论在儿童心肌病患者中常规进行串联质谱检查有助于肉碱缺乏症的诊断；对于肉碱缺乏所致心肌病患儿采用左旋肉碱治疗可获得良好的效果。

Objective Carnitine deficiency has been associated with progressive cardiomyopathy due to compromised energy metabolism. The objective of this study was to investigate clinical features of carnitine deficiency-induced cardiomyopathy and the therapeutic efficacy of L-carnitine administration. Method Between January 2010 and December 2011, filter-paper blood spots were collected from 75 children with cardiomyopathy. Free carnitine and acylcarnitine profiles were measured for each individual by tandem mass spectrometry （MS/MS）. For those in whom carnitine deficiency was demonstrated, treatment was begun with L-carnitine at a dose of 150 -250 rag/（ kg .d）. Clinical evaluation, including physical examination, electrocardiography, chest x-ray, echocardiography and tandem mass spectrometry, was performed before therapy and during follow-up. Result Of 75 cardiomyopathy patients, the diagnosis of carnitine deficiency was confirmed in 6 patients, which included 1 boy and 5 girls. Their age ranged from 0. 75 to 6 years. Free carnitine content was （ 1.55 ±0. 61 ） μmol/L （reference range 10-60 μmol/L）. Left ventricular end-diastolic diameter （LVDd） was （5.04 ± 0. 66 ） cm and left ventricular ejection fraction （LVEF） was （38.5 ± 10. 5）%. After 10-30 d therapy of L-carnitine, free carnitine content rose to （30. 59 ±15.02） μmol/L（ t = 4. 79, P 〈 0. 01 ）. LVDd decreased to （4.42 ± 0. 67 ） cm （ t = 4. 28, P 〈 0. 01 ） and LVEF increased to （49. 1 ± 7.6 ） % （ t = 6. 59, P 〈0. 01 ）. All patients received follow-up evaluations beyond 6 months of treatment. Clinical improvement was dramatic. LVEF returned to normal completely in all the 6 patients. LVDd decreased further in all the 6 patients and returned to normal levels in 3 patients. No clinical signs or symptoms were present in any of the 6 patients. The only complications of therapy had been intermittent diarrhea in 1 patient. Conclusion Tandem mass spectrometry is helpful to diagnose carnitinedeficiency and should be performed in all children with cardiomyopathy. L-carnitine has a good therapeutic effect on carnitine deficiency-induced cardiomyopathy.