目的 探讨孕母甲状腺疾病的新生儿第一个月生长速率和甲状腺功能与2岁时神经发育结局之间的相关性。方法 2013年1月—2014年12月在我院出生的156例孕母甲状腺疾病的新生儿为实验组,观察其第1个月体质量、身长及头围生长的速率,生后当天、第7天、第28天的总甲状腺素(TT4)及促甲状腺素(TSH)的水平;妊娠期无高危因素的母亲分娩的正常新生儿中随机抽取150例为正常对照组,观察生后新生儿第1个月体质量、身长及头围生长的速率,2组均在2岁内分别每3个月均接受随访评估,2岁时行贝利婴幼儿发展量表进行Bailey智力发育指数(MDI)、精神运动发育指数(PDI)的评分。采用回归分析检验新生儿生后第一个月体质量、身长及头围生长的速率,新生儿生后当天、第7天、第28天的TT4及TSH水平与中位数的差值与2岁时MDI、PDI之间的关联性。结果 ①实验组生后第1个月体质量(29.5±4.2 g/d)、身长(1.18±0.67 cm/周)及头围(0.79±0.39 cm/周)生长的速率慢于正常对照组的体质量(35.4±6.3 g/d)、身长(1.69±0.85 cm/周)及头围(1.10±0.42 cm/周)生长的速率,2组差异有统计学意义(t值分别为9.672、5.882、6.768,P均<0.05);②实验组2岁时MDI(108±15)、PDI评分(109±16)低于正常对照组MDI(115±14)、PDI评分(118±11),2组差异有统计学意义(t值分别为16.129、21.279,P均<0.05);③实验组孕母甲状腺疾病的新生儿生后第1个月体质量、身长及头围生长的速率与2岁时MDI、PDI呈正相关(相关系数分别为:0.874,0.842,0.890,0.857,0.871,0.845,t值分别为22.584,59.296,65.441,61.214,62.662,59.507,P均<0.05);④实验组孕母甲状腺疾病的新生儿生后当天、第7天及第28天的TT4及TSH水平与中位数的差值与2岁时MDI、PDI呈负相关(相关系数分别为:-0.878,-0.894,-0.890,-0.690,-0.654,-0.702,t值分别为73.167,81.273,74.166,11.523,10.548,12.103,P均<0.05)。结论 母亲妊娠期患有甲状腺疾病会影响新生儿生后第1个月体质量、身长、头围生长的速率及2岁时的精神运动、智力发育,落后于母亲妊娠期无高危疾病的正常新生儿。另外孕母甲状腺疾病的新生儿第1个月体质量、身长及头围生长的速率和生后当天、生后第7天 及第28天的T4及TSH的水平与2岁时MDI、PDI密切相关。

Objective To investigate the correlation between the growth rate, thyroid function in the first month and neurodevelopmental outcome at the age of 2 in the infants of the maternal thyroid disease. Methods We chose 156 infants of maternal thyroid disease from January 2013 to December 2014 born in our hospital as the experimental group and 150 normal infants of their mothers without high risk factors during pregnancy as the control group. We observed the rate of weight, length and head circumference growth in the first month and TT4 、TSH level at the 1^st day, 7^th day, and 28^th day after birth. We followed up two groups every 3 months up to the age of 2. We assessed Bailey mental development index (MDI) and psychomotor development index (PDI) at the age of 2. Regression analysis was used to test the correlation between the growth rate, TT4,TSH level in the 1^st month and MDI, PDI at the age of 2. Results ① The rate of growth rate in the 1^st month of the experimental group was slower than the control group. It was statistically significant difference between the two groups (P<0.05); ②MDI, PDI at the age of 2 in the experimental group were lower than those of the control group. It was statistically significant difference between the two groups (P<0.05); ③The rate of growth rate in the first month of the experimental group was positively related to MDI and PDI at the age of 2.④The difference between the level of TT4,TSH at the 1^st day, 7thday, and 28^th day and the median after birth was negatively related to MDI and PDI at the age of 2. Conclusion The maternal thyroid disease will affect the first month growth rate and neurodevelopmental outcome at the age of 2 of their infants. Their infants will grow behind than the normal newborns on pregnancy without high-risk disease.The growth rate of the first month and the level of T4 and TSH on the 1^st day, 7^th day, and 28^th day in maternal thyroid disease are closely related MDI and PDI at the age of 2.

目的 探讨原发性肉碱缺乏症的诊断与治疗方案,对2例原发性肉碱缺乏症患儿及其家系行SLC22A5基因检测,确定基因突变位点,为家系提供遗传疾病的咨询。方法 用串联质谱技术对1例疑似患儿进行游离肉碱及多种酰基肉碱检测,对游离肉碱降低的患儿行SLC22A5基因突变检测,确诊PCD,对其姐姐行上述检查。对2例确诊PCD患儿补充左旋肉碱治疗,随访11个月。并对其家系行SLC22A5基因检测。结果 2例确诊PCD患儿,1例为临床患儿,另1例为其姐姐,无明显临床表现。2例患儿均检测到基因突变。2例患儿血游离肉碱水平低于参考值,伴多种酰基肉碱显著降低,均给予补充左旋肉碱治疗,1例治疗2月后症状改善,另1例未曾未发病,血游离肉碱及其他酰基肉碱水平上升至正常。2例患儿SLC22A5 c.760C>T,(p.Arg254X)纯合,致病突变;患儿父母亲SLC22A5基因的c.760C位点检测,发现:均携带c.760C>T,(p.Arg254X)杂合突变。结论 应用串联质谱技术检测血游离肉碱、多种酰基肉碱水平及SLA22A5基因突变检测诊断了2例PCD,均补充左旋肉碱取得较好疗效。SLC22A5基因c.760C>T,(p.Arg254X)突变是本家系中患有PCD的致病突变,用错义突变和剪切改变的分析手段对SLC22A5基因的外显子编码区进行直接测序可为PCD家系提供遗传咨询。

Objective To explore the diagnosis and treatment of primary carnitine deficiency. To identify potential mutation of SLC22A5 gene in two children affected with primary carnitine deficiency and provide genetic counseling. Methods We measured the free camitine(Co)and acylcamitine levels in a suspected clinical inherited metabolic diseases by tandem mass spectrometry. The SLC22A5 gene mutations were tested to the children with low Co level and the diagnosis was made. Then, We measured the free camitine(Co)and acylcamitine levels and SLC22A5 gene mutations in her sister. The children with PCD were treated with carnitine and followed up for 11 months. The SLC22A5 gene was detected in their family. Results In two children affected with PCD, 1 case was clinical children, another case of their sister was no obvious clinical manifestations. Mutations were found in all of them.The average C0 level in patients was lower than the reference value,along with decreased level of different acylcamitines. Two cases were treated with earnitine. Their clinical symptoms reduced 2 months later. Another case had not been sick. The CO level and different acylcamitines level in the blood rose to normal. A homozygous mutation C. 760C>T (P. Arg254X)of the SLC22A5 gene was detected in the two cases.Heterozygous mutation C. 760C>T (P.Arg254X) was also found in other family members. Conclusion Two patients were diagnosed with PCD by the test levels of free carnitine and acylcarnitines in blood with tandem mass spectrometry,and gene mutation test. L-carnitine supplement had a good effect in treatment of the PCD patients.C.760C> T (P.Arg254X) mutations of the SLC22A5 gene is the deleterious mutations for PCD families, The analysis method of the wrong mutagenesis and shear changes which is used to directly sequence the exons codes of the SLC22A5 gene can provide genetic counseling for PCD families.