2020 年第 12 期 第 15 卷

同型半胱氨酸在新生儿疾病筛查中的应用

Application of homocysteine in screening for neonatal diseases

作者：杨铭华姜玥竹李津津崔颖潘湘萍

英文作者：Yang Minghua Jiang Yuezhu Li Jinjin Cui Ying Pan Xiangping

单位：哈尔滨市儿童医院检验科150010

英文单位：Department of Laboratory Harbin Children′s Hospital Harbin 150010 China

关键词：新生儿筛查；同型半胱氨酸；遗传代谢性疾病

英文关键词：Neonatalscreening;Homocysteine;Hereditarymetabolicdisease

• 摘要：

• 目的 探讨血清同型半胱氨酸（Hcy）在新生儿疾病筛查中的应用价值。方法 选取2010年8月至2017年9月哈尔滨市儿童医院收治的95例患儿。其中遗传代谢性疾病31例，包括甲基丙二酸尿症（MMA）7例，MMA合并高Hcy血症24例；新生儿缺氧缺血性脑病43例（轻度12例、中度18例、重度13例）；先天性甲状腺功能低下症21例。选择同期本院产科出生的34名正常新生儿为对照组。采用自动生化分析仪检测血清Hcy水平，酶联免疫法检测血清肌酸激酶和肌酸激酶同工酶BB（CK-BB）水平，气相色谱-质谱联用分析法分析尿液甲基丙二酸浓度，放射免疫法检测新生儿血清叶酸水平，化学发光免疫系统检测血清促甲状腺激素（TSH）和游离甲状腺素（FT4）水平。结果 轻、中、重度组新生儿缺氧缺血性脑病患儿血清Hcy、肌酸激酶和CK-BB水平均明显高于对照组［（13.8±1.8）、（20.2±3.7）、（30.6±6.9）μmol/L比（9.1±0.9）μmol/L；（422±88）、（699±158）、（744±178）U/L比（87±11）U/L；（16.4±2.5）、（18.3±4.7）、（27.6±7.7）U/L比（7.3±1.2）U/L］，差异均有统计学意义（均P＜0.05）。MMA组、MMA合并高Hcy血症组患儿尿液甲基丙二酸水平均明显高于对照组（均P＜0.05），3组血清叶酸水平比较差异无统计学意义（P＞0.05）。MMA合并高Hcy血症组血清Hcy水平高于对照组和MMA组（均P＜0.05）。新生儿先天性甲状腺功能低下患儿血清Hcy、TSH水平明显高于对照组，FT4水平明显低于对照组（均P＜0.01）。结论 在新生儿疾病筛查项目中增加血清Hcy的检测，对于遗传代谢性疾病的诊断及治疗方案的制定都有着积极意义。

• Objective To explore the clinical diagnosis value of serum homocysteine(Hcy)  in the neonatal diseases screening. Methods From August 2010 to September 2017, 95 children with birth defects admitted to Harbin Children′s Hospital were selected. There were 31 cases with inherited metabolic diseases (IMD), including 7 cases with methylmalonic aciduria(MMA), 24 cases with MMA complicated with hyperhomocysteinemia (HHcy), 43 cases with neonatal hypoxic ischemic encephalopathy(12 cases of a mild degree, 18 cases of a moderate degree and 13 cases of a severe degree) and 21 cases with congenital hypothyroidism. Thirty-four normal newborns borned in the obstetrics department of our hospital during the same period were selected as control group. Automatic biochemical analyzer was utilized to detect serum Hcy level. Serum creatine kinase(CK) and CK-BB levels were detected with enzyme linked immunosorbent assay, and urine methylmalonic acid concentration with gas chromatography-mass spectrometry, neonatal blood folate levels with radioimmunoassay, serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels with chemiluminescence immune system. Results The Hcy, CK and CK-BB levels of neonates with hypoxic-ischemic encephalopathy in the mild, moderate and severe groups were higher than those in control group［(13.8±1.8),(20.2±3.7),(30.6±6.9)μmol/L vs (9.1±0.9)μmol/L；(422±88),(699±158),(744±178)U/L vs (87±11)U/L；(16.4±2.5),(18.3±4.7),(27.6±7.7)U/L vs (7.3±1.2)U/L］(all P＜0.05). The levels of methylmalonic acid in the MMA group and MMA complicated with HHcy group were significantly higher than those in control group (both P＜0.05). There was no statistically significant difference in folic acid levels among the three groups (P>0.05). The Hcy levels in the MMA complicated with HHcy group was higher than that in the control and the MMA group,respectively (both P＜0.05). The Hcy and TSH levels in neonatal children with congenital hypothyroidism were higher than those in control group, whereas FT4 level was lower, all with statistically significant differences (all P＜0.01). Conclusion Testing Hcy during neonatal screening can provide a reference for effectively monitoring genetic metabolic diseases, therapeutic decision-making and prognosis of neonatal disease.