Mass Spectrometry Center, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Mass Spectrometry Center, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal; CESAM - Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Arch Biochem Biophys. 2020 Jul 30;688:108431. doi: 10.1016/j.abb.2020.108431. Epub 2020 May 24.
Phenylketonuria (PKU) is the most prevalent inborn error of amino acid metabolism. The disease is due to the deficiency of phenylalanine (Phe) hydroxylase activity, which causes the accumulation of Phe. Early diagnosis through neonatal screening is essential for early treatment implementation, avoiding cognitive impairment and other irreversible sequelae. Treatment is based on Phe restriction in the diet that should be maintained throughout life. High dietary restrictions can lead to imbalances in specific nutrients, notably lipids. Previous studies in PKU patients revealed changes in levels of plasma/serum lipoprotein lipids, as well as in fatty acid profile of plasma and red blood cells. Most studies showed a decrease in important polyunsaturated fatty acids, namely DHA (22:6n-3), AA (20:4n-6) and EPA (20:5n-6). Increased oxidative stress and subsequent lipid peroxidation have also been observed in PKU. Despite the evidences that the lipid profile is changed in PKU patients, more studies are needed to understand in detail how lipidome is affected. As highlighted in this review, mass spectrometry-based lipidomics is a promising approach to evaluate the effect of the diet restrictions on lipid metabolism in PKU patients, monitor their outcome, namely concerning the risk for other chronic diseases, and find possible prognosis biomarkers.
苯丙酮尿症（PKU）是最常见的氨基酸代谢遗传缺陷病。这种疾病是由于苯丙氨酸（Phe）羟化酶活性缺乏，导致 Phe 积累而引起的。通过新生儿筛查早期诊断对于早期实施治疗至关重要，可以避免认知障碍和其他不可逆转的后遗症。治疗基于饮食中限制 Phe，这种限制应贯穿一生。高饮食限制可能导致特定营养素（尤其是脂质）的不平衡。以前的 PKU 患者研究显示了血浆/血清脂蛋白脂质水平以及血浆和红细胞中脂肪酸谱的变化。大多数研究表明，一些重要的多不饱和脂肪酸（即 DHA[22:6n-3]、AA[20:4n-6]和 EPA[20:5n-6]）的含量下降。PKU 中还观察到氧化应激增加和随后的脂质过氧化。尽管有证据表明 PKU 患者的脂质谱发生了变化，但仍需要更多的研究来详细了解脂质组如何受到影响。正如本综述所强调的，基于质谱的脂质组学是评估饮食限制对 PKU 患者脂质代谢影响的一种很有前途的方法，可以监测他们的治疗效果，特别是关于其他慢性疾病的风险，并寻找可能的预后生物标志物。
