标题：新生儿遗传罕见病的早期识别和病因分析

      作者：崔清洋 1，张明霞 2，井秀杰 3，石计朋 4，桑桂梅 1，孙亚洲 1，唐成和 1，李树军 1，逯军 5    1.新乡医学院第一附属医院儿科， 河南 卫辉 453100；2.新乡市妇幼保健院新生儿科，河南 新乡 453003；3.泰安市中心医院新生儿科，山东 泰安 271099；4.佛山市妇幼保健院新生儿科，广东 佛山 528000；5.广东医科大学附属医院儿童医学中心，广东 湛江 524000

      卷次： 2023年34卷21期

      【摘要】 目的 研究新生儿遗传罕见病的早期识别及诊断方法。方法 回顾性分析2014—2022年新乡医学院第一附属医院新生儿科、新乡市妇幼保健院新生儿科、泰安市中心医院新生儿科及佛山市妇幼保健院新生儿科收治的82例遗传罕见病病例的临床资料、实验室检查及基因检测结果。结果 82例遗传罕见病中肝脏疾病15例(鸟氨酸氨甲酰基转移酶缺乏症 3例，氨甲酰磷酸合成酶 I缺乏症 2例，氨甲酰磷酸合成酶 I缺乏症或鸟氨酸氨甲酰基转移酶缺乏症 1例，吉尔伯特综合征 6例，钠牛磺胆酸共转运多肽缺陷病 2例，低碱性磷酸酶血症 1例)，神经肌肉疾病 17例(早发性脑病 5例，良性家族性新生儿癫痫 5例，钼辅因子缺乏症A型 1例，先天性肌无力综合征 5型 1例，7型杆状体肌病 1例，3型杆状体肌病 1例，Miller?Dieker综合征 1例；德朗热综合征 1例，PURA综合征1例)，呼吸系统疾病1例(先天性中枢低通气综合征)，泌尿系统疾病5例(巴特综合征3型3例，先天性肾病综合征2例)，遗传代谢病23例(甲基丙二酸血症12例，高草酸尿症2例，极长链酰基辅酶A脱氢酶缺乏症1例，异戊酸血症2例，枫糖尿病1例，核基因变异所致新生儿原发性线粒体病4例，糖原累积症Ⅱ型1例)，免疫缺陷7例(重症联合免疫缺陷1例，22q11.2微缺失综合征5例，湿疹-血小板减少伴免疫缺陷综合征1例)，皮肤疾病2例(SAM综合征1例；色素失禁症1例)，内分泌疾病4例(甲状腺激素合成障碍性先天性甲减2例，先天性肾性尿崩症2例)，微缺失或微重复1例(16p11.2微缺失综合征)，表观遗传病2例(Beckwith?Wiedemann综合征1例；Prader?Willi 综合征1例)，涉及多个系统疾病5例(复合型甘油酸激酶缺乏症1例，CHARGE综合征2例，努南综合征5型1例，努南综合征8型1例)。结论 新生儿遗传罕见病涉及多系统，对体格检查、实验室检查、彩超及头颅MRI异常进行综合判断，积极给予血串联质谱、尿气相色谱-质谱筛查和基因检测有助于早期发现新生儿遗传罕见病。
      【关键词】 遗传罕见病；新生儿；串联质谱；气相色谱-质谱；基因检测
      【中图分类号】 R722.11 【文献标识码】 A 【文章编号】 1003—6350（2023）21—3119—04

Early identification and etiological analysis of genetic rare diseases in newborns.
CUI Qing-yang 1, ZHANGMing-xia 2, JING Xiu-jie 3, SHI Ji-peng 4, SANG Gui-mei 1, SUN Ya-zhou 1, TANG Cheng-he 1, LI Shu-jun 1, LU Jun 5. 1.Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan, CHINA; 2.Department of Neonatology, Xinxiang Maternal and Child Health Hospital, Xinxiang 453003, Henan, CHINA; 3.Department of Neonatology, Tai'an Central Hospital, Tai'an 271099, Shandong, CHINA; 4. Department of Neonatology,Foshan Maternal and Child Health Hospital, Foshan 528000, Guangdong, CHINA; 5. Children's Medical Center, AffiliatedHospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, CHINA
【Abstract】 Objective To study the early identification and diagnosis of neonatal genetic rare diseases.Methods The clinical data, laboratory examination, and genetic test results of 82 neonates of genetic rare disease ad?mitted to the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical College; Department of Neo?natology, Xinxiang Maternal and Child Health Care Hospital; Department of Neonatology, Tai'an Central Hospital; andDepartment of Neonatology, Foshan Maternal and Child Health Care Hospital from 2014 to 2022 were retrospectivelyanalyzed. Results Among the 82 cases of genetic rare diseases, there were 15 cases of liver diseases (3 cases of orni?thine carbamoyltransferase deficiency; 2 cases of carbamyl phosphate synthetase I deficiency; 1 case of carbamyl phos?phate synthetase I deficiency or ornithine carbamoyltransferase deficiency; 6 cases of Gilbert syndrome; 2 cases of sodiumtaurocholic acid co?transport peptide deficiency disease; 1 case of hypoalkaline phosphatase anemia), 17 cases of neuro?muscular diseases (5 cases of early?onset encephalopathy; 5 cases of benign familial neonatal epilepsy; 1 case of molybde?num cofactor deficiency type A; 1 case of congenital myasthenia syndrome type 5; 1 case of type 7 rod?shaped myopathy;1 case of type 3 rod?shaped myopathy; 1 case of Miller?Dieker syndrome; 1 case of De Lange syndrome; 1 case of PU?RA syndrome), 1 case of respiratory diseases (congenital central hypopnea syndrome), 5 cases of urinary system diseases(3 cases of Barthes syndrome type 3; 2 cases of congenital nephrotic syndrome), 23 cases of hereditary metabolic diseas?es (12 cases of methylmalonic acidemia; 2 cases of hyperoxaluria; 1 case of extremely long chain acyl CoA dehydroge?nase deficiency; 2 cases of isovaleric acidemia; 1 case of maple diabetes; 4 cases of neonatal primary mitochondrial dis?ease caused by nuclear gene mutations; 1 case of glycogen accumulation syndrome type Ⅱ), 7 case of immunodeficien?cy (1 case of severe combined immunodeficiency; 5 cases of 22q11.2 microdeletion syndrome; 1 case of eczema throm?bocytopenia with immunodeficiency syndrome), 2 cases of skin diseases (1 case of SAM syndrome; 1 case of pigmentincontinence), 4 cases of endocrine diseases (2 cases of congenital hypothyroidism with thyroid hormone synthesis disor?ders; 2 case of congenital renal diabetes insipidus), 1 case of microdeletion or microduplication (16p11.2 microdeletionsyndrome), 2 cases of epigenetic diseases (1 case of Beckwith?Wiedemann syndrome; 1 case of Prader?Willi syndrome),5 cases involving multiple systemic diseases (1 case of complex glycerate kinase deficiency; 2 cases of CHARGE syn?drome; 1 case of Noonan syndrome type 5; 1 case of Noonan syndrome type 8). Conclusion Genetic rare diseases ofnewborns involve multiple systems. Comprehensive evaluation of physical examination, laboratory examination, colorultrasound, and head MRI abnormalities, as well as active blood tandem mass spectrometry, urine gas chromatograms,mass spectrometry screening, and genetic testing are helpful for early detection of neonatal genetic rare diseases.
      【Key words】 Genetic rare disease; Newborns; Tandem mass spectrometry; Gas chromatography?mass spectrome?try; Genetic testing