PDF(Pubmed)
Abstract：
Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients.
To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers.
In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms.
Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.
To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers.
In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms.
Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.
摘要：
苯丙酮尿症（PKU）通常被认为是遗传性疾病的经典例子，如今可以通过早期诊断和治疗成功预防严重症状。相比之下,众所周知，未经治疗或后期治疗的PKU会导致严重的智力残疾，癫痫发作,和行为障碍。很少,然而,据报道,血浆苯丙氨酸浓度高的未经治疗或晚期诊断的PKU患者可避免智力障碍.本研究旨在回顾已发表的此类PKU患者的病例。
为此,截至2017年9月8日,我们在PubMed和EMBASE进行了文献检索,以确定以下情况:1)7岁后PKU诊断和开始治疗;2)未经治疗的血浆苯丙氨酸浓度≥1200μmol/l;3)IQ≥80.文献检索,检查参考列表，选择的文章，数据提取由两名独立研究人员完成.
总共，我们确定了59例符合纳入标准的晚期诊断PKU和意外有利结局的患者.尽管所有被调查患者的智力功能都在正常范围内，至少有19人表现出其他神经系统，心理,和/或行为症状。
根据目前的发现，未经治疗或晚期治疗的PKU的经典症状可能需要重写，不仅在智力功能障碍不是强制性的意义上，但也在这个意义上，智力功能不（重新）呈现脑损伤的全貌，由于高血浆苯丙氨酸浓度。为了更好地了解PKU患者之间的这些差异，需要进一步识别此类患者并进行其他分析。
为此,截至2017年9月8日,我们在PubMed和EMBASE进行了文献检索,以确定以下情况:1)7岁后PKU诊断和开始治疗;2)未经治疗的血浆苯丙氨酸浓度≥1200μmol/l;3)IQ≥80.文献检索,检查参考列表，选择的文章，数据提取由两名独立研究人员完成.
总共，我们确定了59例符合纳入标准的晚期诊断PKU和意外有利结局的患者.尽管所有被调查患者的智力功能都在正常范围内，至少有19人表现出其他神经系统，心理,和/或行为症状。
根据目前的发现，未经治疗或晚期治疗的PKU的经典症状可能需要重写，不仅在智力功能障碍不是强制性的意义上，但也在这个意义上，智力功能不（重新）呈现脑损伤的全貌，由于高血浆苯丙氨酸浓度。为了更好地了解PKU患者之间的这些差异，需要进一步识别此类患者并进行其他分析。
