高苯丙氨酸血症遗传分型与诊治

doi:10.12372/jcp.2023.22e1525

临床儿科杂志 ›› 2023, Vol. 41 ›› Issue (2): 92-97.doi: 10.12372/jcp.2023.22e1525

高苯丙氨酸血症遗传分型与诊治

梁黎黎

上海交通大学医学院附属新华医院儿内分泌遗传科上海市儿科医学研究所（上海 200092）

收稿日期:2022-11-15 出版日期:2023-02-15 发布日期:2023-02-16
作者简介:梁黎黎，医学博士，青年编委，ORCID：0000-0002-7610-9825。上海交通大学医学院附属新华医院儿内分泌遗传代谢专业副主任医师，美国波士顿儿童医院访问学者，《临床儿科杂志》青年编委。主要从事遗传代谢病和儿内分泌疾病的临床和基础研究。主持国家自然科学基金及市级课题4项，参与科技部重大课题2项，以第一或通信作者发表SCI论文十余篇。
基金资助:
上海市卫生健康委员会面上项目(202040448)

Genetic classification, diagnosis, and treatment of hyperphenylalaninemia

LIANG Lili

Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China

Received:2022-11-15 Online:2023-02-15 Published:2023-02-16

摘要/Abstract

摘要：

高苯丙氨酸血症是一组常染色体隐性遗传氨基酸代谢病，由苯丙氨酸羟化酶及其辅酶四氢生物蝶呤缺陷引起，如不及时治疗将出现严重的神经系统损害，治疗以低苯丙氨酸饮食疗法和补充神经递质药物为主。我国于1982年开始进行高苯丙氨酸血症的新生儿筛查，越来越多的患者在新生儿疾病筛查过程中确诊。高苯丙氨酸血症的诊断已经从临床症状的诊断向新生儿期无症状的生化和基因诊断转变。如何对高苯丙氨酸血症患者进行早期识别和诊治，已然成为临床医师面临的新挑战。文章主要对高苯丙氨酸血症的遗传背景、诊断、鉴别诊断与治疗进行阐述，以提高临床医师对此疾病的认识。

关键词: 苯丙氨酸羟化酶, 高苯丙氨酸血症, 四氢生物喋呤, 新生儿疾病筛查

Abstract:

Hyperphenylalaninemia is a group of autosomal recessive amino acid metabolic disorders, caused by defects in phenylalanine hydroxylase and its coenzyme tetrahydrobiopterin. If left untreated, severe neurological damage will occur. Treatment is based on low-phenylalanine diet therapy and neurotransmitter drug supplementation. Newborn screening for hyperphenylalaninemia began in China in 1982, more and more patients are being diagnosed during the screening. The diagnosis of hyperphenylalaninemia has shifted from the diagnosis of clinical symptoms to biochemical and genetic diagnosis in asymptomatic period. The early differential diagnosis and proper treatment for patients with hyperphenylalaninemia has become a new challenge for clinicians. Therefore, the article focuses on the genetic background, diagnosis, differential diagnosis and treatment of hyperphenylalaninemia, to raise the awareness for the disease among clinicians.

Key words: phenylalanine hydroxylase, hyperphenylalaninemia, tetrahydrobiopterin, newborn screening

梁黎黎. 高苯丙氨酸血症遗传分型与诊治[J]. 临床儿科杂志, 2023, 41(2): 92-97.

LIANG Lili. Genetic classification, diagnosis, and treatment of hyperphenylalaninemia[J]. Journal of Clinical Pediatrics, 2023, 41(2): 92-97.

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参考文献 29

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缺陷类别	致病基因	BH4反应性	尿蝶呤谱	DHPR活性	治疗
苯丙氨酸羟化酶缺乏症 BH4缺乏症	PAH	部分患者有反应	正常	正常	低苯丙氨酸饮食、BH4
鸟苷三磷酸环化水解酶缺乏症	GCH1	有反应	新喋呤降低，生物蝶呤降低	正常	BH4、左旋多巴、5-羟色胺
6-丙酮酰四氢蝶呤合成酶缺乏症	PTS	有反应	新喋呤增高，生物蝶呤降低	正常	BH4、左旋多巴、5-羟色胺
墨蝶呤还原酶缺乏症	SPR	有反应	新喋呤增高，生物蝶呤增高	正常	左旋多巴、5-羟色胺
蝶呤-4α-甲醇氨脱水酶缺乏症	PCBD	有反应	新喋呤增高，生物蝶呤正常/降低	正常	BH4,或不需要治疗
二氢蝶啶还原酶缺乏症	QDPR	有反应	新喋呤正常，生物蝶呤正常/增高	降低	低苯丙氨酸饮食、四氢叶酸、左旋多巴、5-羟色胺
苯丙氨酸羟化酶单体折叠缺陷	DNAJC12	有反应	正常	正常	低苯丙氨酸饮食、BH4、左旋多巴、5-羟色胺

高苯丙氨酸血症遗传分型与诊治

Genetic classification, diagnosis, and treatment of hyperphenylalaninemia

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