原发性肉碱缺乏症17例诊治与随访

Primary carnitine deficiency in 17 patients： diagnosis, treatment and follow up

目的探讨原发性肉碱缺乏症的诊断与治疗。方法利用串联质谱技术对27万例新生儿和1．2万例临床遗传代谢病疑似患儿进行游离肉碱及酰基肉碱检测，对游离肉碱降低的患儿进行肉碱转运蛋白基因突变检测确诊。对确诊患儿给予左旋肉碱治疗，100-300mg／（kg·d），分3次静滴或口服。随访时间3个月-3年。结果共确诊17例原发性肉碱缺乏症患儿，其中6例来自新生儿筛查，11例来自临床患儿。17例患儿均检测到基因突变。患儿血游离肉碱水平[（2．85±1．87）μmol／L]低于参考值（10μmol／L），伴不同种类的酰基肉碱水平下降。治疗随访14例，给予左旋肉碱治疗1-3个月后，临床症状消失，血游离肉碱升至正常，由（2．91±2．01）μmol／L升至（20．63±8．32）μmol／L，其他酰基肉碱也升至正常。结论采用串联质谱技术检测血游离肉碱、酰基肉碱水平及肉碱转运蛋白基因检测诊断了17例原发性肉碱缺乏症患儿，其中14例患儿经大剂量左旋肉碱治疗获得了较好的疗效。

Objective Many children were found to have low free carnitine level in blood by tandem mass spectrometry technology. In some of the cases the problems occurred secondary to malnutrition, organic acidemia and other fatty acid oxidation metabolic diseases, and some of cases had primary carnitine deficiency （PCD）. In the present article, we discuss the diagnosis of PCD and evaluate the efficacy of earnitine in the treatment of PCD. Method We measured the free earnitine （C0） and aeylearnitine levels in the blood of 270 000 neonates from newborns screening program and 12 000 children with suspected clinical inherited metabolic diseases by tandem mass spectrometry. The mutations of carnitine transporter protein were tested to the children with low CO level and the diagnosis was made. The children with PCD were treated with 100-300 mg/kg of carnitine. Result Seventeen children were diagnosed with PCD, 6 from newborn screening program and 11 from clinical patients. Mutations were found in all of them. The average CO level [ （2. 9±2. 0） μmol/L ] in patients was lower than the reference value （ 10 μmol/L） , along with decreased level of different acylearnitines. The clinical manifestations were diverse. For the 6 patients from newborn screening, 4 were asymptomatie, 1 showed hypoglycaemia and 1 showed movement intolerance from 2 years of age. For the 11 clinical patients, 8 showed hepatomegaly, 7 showed myasthenia, 6 showed cardiomyopathy, 1 showed chronic abdominal pain, and 1 showed restlessness and learning difficulty. Among these patients, 14 cases were treated with carnitine. Their clinical symptoms disappeared 1 to 3 months later. The CO level in the blood rose to normal, with the average from （ 4. 0 ± 2. 7 ） μmol/L to （20. 6 ±8.3） μmol/L （P 〈 0. 01 ）. However, the level was still lower than the average level of healthy children [ （27.1 ± 4. 5 ）μmol/L,P 〈 0. 01 ]. Conclusion Seventeen patients were diagnosed with PCD by the test levels of free earnitine and acylearnitines in blood with tandem mass spectrometry, and gene mutation test. Large dose of earnitine had a good effect in treatment of the PCD patients.