Inherited Metabolic Diseases Division, Regional Center for Expanded Neonatal Screening, Women and Children's Health Department, University Hospital of Padua, Padua, Italy.
Department of Human Neuroscience, Unit of Child Neurology and Psychiatry, University La Sapienza, Rome, Italy.
Curr Med Res Opin. 2021 Mar;37(3):411-421. doi: 10.1080/03007995.2020.1847717. Epub 2021 Feb 1.
Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase (PAH). Its prevalence is estimated to be 1:10,000 in Europe. PKU is the commonest congenital inborn error of metabolism. The aim of our study was to investigate the characteristics of clinical practice in relation to PKU in Italy, in order to raise awareness about the current management and therapeutic approaches adopted.
Six Italian experts conducted a systematic literature review as well as an internal survey to investigate the relevant clinical aspects. Collectively, the expert panel managed a total of 678 PKU patients treated in the early stages of the condition over a 16-year period across six centers.
The management of PKU varied markedly between centers, with differences in the composition of the multidisciplinary team, dietary treatments, compliance and adherence to management, tetrahydrobiopterin use, and patient follow-up. Patients were mostly managed by a pediatric reference center from the initial PKU diagnosis during newborn screening until adulthood, without transition to a specialized adult clinician. Fogginess, concentration reduction, low attention, anxiety, irritability, memory deficit, headache, and unstable mood were common features in patients with uncontrolled blood phenylalanine levels (generally above 600 µmol/L).
A homogeneous and shared approach to the management of PKU patients is important. Our survey demonstrates the current management of PKU in Italy, with the aim of promoting the implementation of therapeutic strategies and follow-up, increased patient compliance and adherence, and the achievement of the phenylalanine level targets recommended by European Union guidelines. Emerging therapies are likely to become a standard treatment for patients unable to comply with diet therapy and maintain their phenylalanine levels below the threshold values.
Supplemental data for this article is available online at https://doi.org/10.1080/03007995.2020.1847717.
苯丙酮尿症（PKU）是一种由苯丙氨酸羟化酶（PAH）缺乏引起的罕见常染色体隐性遗传疾病。据估计，在欧洲其患病率为 1:10000。PKU 是最常见的先天性代谢缺陷。我们研究的目的是调查意大利 PKU 临床实践的特点，以提高对当前管理和治疗方法的认识。
六位意大利专家进行了系统的文献复习和内部调查，以研究相关的临床方面。专家组总共管理了 678 名在六个中心接受治疗的 PKU 患者，这些患者在疾病早期接受治疗的时间长达 16 年。
PKU 的管理在各中心之间存在显著差异，包括多学科团队的组成、饮食治疗、对管理的依从性、四氢生物蝶呤的使用以及患者的随访存在差异。患者大多由儿科参考中心从新生儿筛查时的初始 PKU 诊断开始管理，直至成年，没有过渡到专门的成年临床医生。在未控制的血苯丙氨酸水平（通常高于 600μmol/L）的患者中，常出现模糊、注意力减少、注意力不集中、焦虑、易怒、记忆力减退、头痛和情绪不稳定等症状。
对 PKU 患者进行统一和共享的管理非常重要。我们的调查展示了意大利目前 PKU 的管理情况，旨在促进治疗策略和随访的实施、提高患者的依从性和一致性，并达到欧盟指南推荐的苯丙氨酸水平目标。对于无法遵守饮食治疗并将其血苯丙氨酸水平保持在阈值以下的患者，新出现的治疗方法可能成为标准治疗。
