Department of Clinical Nutrition & Dietetics Agia Sofia Children's Hospital, Athens, Greece.
Department of Pharmacy, Laboratory of Pharm. Analysis, National and Kapodestrian University of Athens, Panepistimiopolis Zographou, GR 157 71, Athens, Greece.
Nutr Neurosci. 2020 Aug;23(8):628-639. doi: 10.1080/1028415X.2018.1538196. Epub 2018 Oct 25.
Phenylalanine hydroxylase (PAH) deficiency, commonly named phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism inherited with an autosomal recessive trait. It is characterized by high blood and cerebral Phe levels, resulting in intellectual disabilities, seizures, etc. Early diagnosis and treatment of the patients prevent major neuro-cognitive deficits. Treatment consists of a lifelong restriction of Phe intake, combined with the supplementation of special medical foods, such as Amino Acid medical food (AA-mf), enriched in tyrosine (Tyr) and other amino acids and nutrients to avoid nutritional deficits. Developmental and neurocognitive outcomes for patients, however, remain suboptimal, especially when adherence to the demanding diet is poor. Additions to treatment include new, more palatable foods, based on Glycomacropeptide that contains limited amounts of Phe, the administration of large neutral amino acids to prevent phenylalanine entry into the brain and tetrahydrobiopterin cofactor capable of increasing residual PAH activity. Moreover, further efforts are underway to develop an oral therapy containing phenylalanine ammonia-lyase. Nutritional support of PKU future mothers (maternal PKU) is also discussed. This review aims to summarize the current literature on new PKU treatment strategies.
苯丙氨酸羟化酶(PAH)缺乏症,通常被称为苯丙酮尿症(PKU),是一种常染色体隐性遗传的苯丙氨酸(Phe)代谢紊乱。其特征是血液和大脑中 Phe 水平升高,导致智力残疾、癫痫等。早期诊断和治疗患者可预防主要的神经认知缺陷。治疗包括终身限制 Phe 摄入,同时补充特殊的医疗食品,如富含酪氨酸(Tyr)和其他氨基酸和营养物质的氨基酸医疗食品(AA-mf),以避免营养不足。然而,患者的发育和神经认知结果仍然不理想,尤其是在饮食要求苛刻的情况下依从性较差时。治疗的补充措施包括基于含有有限量 Phe 的糖巨肽的新的、更美味的食物,给予大中性氨基酸以防止 Phe 进入大脑,并添加四氢生物蝶呤辅助因子以增加残余 PAH 活性。此外,还在努力开发一种含有苯丙氨酸氨裂解酶的口服疗法。PKU 未来母亲(母体 PKU)的营养支持也在讨论中。本文旨在总结 PKU 新治疗策略的当前文献。