Phenylketonuria.
Phenylketonuria.
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DOI：
10.1038/s41572-021-00267-0
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发表时间：
2021-05-20
期刊：
影响因子：
--
通讯作者：
Bosch AM
中科院分区：
文献类型：
--
作者：
van Spronsen FJ;Blau N;Harding C;Burlina A;Longo N;Bosch AM
苯丙酮尿症（PKU，又称苯丙氨酸羟化酶（PAH）缺乏症）是一种常染色体隐性苯丙氨酸代谢疾病，特别是高浓度苯丙氨酸可引起脑功能障碍。如果不治疗，这种脑功能障碍会导致严重的智力残疾、癫痫和行为问题。世界各地的患病率各不相同，新生儿的平均患病率约为1:10 000。早期诊断是基于新生儿筛查，如果早期开始治疗并持续治疗，智力在正常范围内，平均而言，一些次优的神经认知功能。饮食限制苯丙氨酸是60多年来治疗的主要方法，并且非常成功，尽管结果仍然不理想，患者可能发现难以坚持治疗。药物治疗是可行的，例如四氢生物蝶呤，仅对少数患者有效（通常是轻度PKU患者），聚乙二醇化苯丙氨酸解氨酶，需要每天皮下注射并引起不良免疫反应。鉴于这些方法的缺点，其他治疗方法正在开发中，如mRNA和基因治疗。尽管多环芳烃缺乏是人类最常见的氨基酸代谢缺陷，但PKU患者的脑功能障碍仍未得到很好的了解，需要进一步研究以促进病理生理驱动治疗的发展。
Phenylketonuria (PKU; also known as phenylalanine hydroxylase (PAH) deficiency) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe intellectual disability, epilepsy and behavioural problems. The prevalence varies worldwide, with an average of about 1:10,000 newborns. Early diagnosis is based on newborn screening, and if treatment is started early and continued, intelligence is within normal limits with, on average, some suboptimal neurocognitive function. Dietary restriction of phenylalanine has been the mainstay of treatment for over 60 years and has been highly successful, although outcomes are still suboptimal and patients can find the treatment difficult to adhere to. Pharmacological treatments are available, such as tetrahydrobiopterin, which is effective in only a minority of patients (usually those with milder PKU), and pegylated phenylalanine ammonia lyase, which requires daily subcutaneous injections and causes adverse immune responses. Given the drawbacks of these approaches, other treatments are in development, such as mRNA and gene therapy. Even though PAH deficiency is the most common defect of amino acid metabolism in humans, brain dysfunction in individuals with PKU is still not well understood and further research is needed to facilitate development of pathophysiology-driven treatments.
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影响因子：
9.8
作者：
Anikster, Yair;Haack, Tobias B.;Schiff, Manuel
通讯作者：
Schiff, Manuel
影响因子：
3.7
作者：
Bosch, Annet M.;Burlina, Alberto;Regnault, Antoine
通讯作者：
Regnault, Antoine
DOI：
10.1001/archpedi.1991.02160010037012
发表时间：
1991-01-01
影响因子：
--
作者：
AZEN, CG;KOCH, R;WARNER, R
通讯作者：
WARNER, R
DOI：
10.1159/000458915
发表时间：
1975-01-01
期刊：
ENZYME
影响因子：
--
作者：
AYLING, JE;HELFAND, GD;PIRSON, WD
通讯作者：
PIRSON, WD
影响因子：
3.7
作者：
Anjema K;Hofstede FC;Bosch AM;Rubio-Gozalbo ME;de Vries MC;Boelen CC;van Rijn M;van Spronsen FJ
通讯作者：
van Spronsen FJ