苯丙酮尿症(PKU)是一种罕见的常染色体隐性遗传疾病,在欧洲影响约1万人,在一些国家有更高的比率,比如爱尔兰和意大利。在意大利,通过MS/MS进行新生儿筛查(NBS)可以诊断怀疑PKU及其变体(高苯丙氨酸血症(HPA),四氢生物蝶呤(BH4)合成缺陷,和四氢生物蝶呤(BH4)再循环缺陷)通过定量干燥血斑(DBS)样品中的苯丙氨酸(Phe)和苯丙氨酸/酪氨酸(Phe/Tyr)比率。这里,我们报告了一例HPA的病例,其怀疑可能与扩大的NBS有关,即使体重正常的新生儿是全胃肠外营养(TPN)。众所周知,TPN可能存在代谢改变,主要用于MS/MS中NBS的氨基酸,经常导致误报。事实上,TPN在NBS中被认为是一种特殊协议,需要几个样本收集。特别是,在TPN之前需要DBS样本,在基础时间点(出生后48小时)和手术结束后72小时。在我们报告的案例中,即使第一个DBS样本(TPN之前)结果为阴性,反复的NBS测试显示,Phe水平升高,Phe/Tyr比率显着升高。因此,新生儿被召回,在HPA怀疑被其他特异性生化试验证实之前,NBS试验重复了几次.这个案例强调了Phe/Tyr比率的重要性,只能通过MS/MS分析检测到,支持新生儿期氨基酸给药期间的诊断怀疑。
Phenylketonuria (PKU) is a rare autosomal recessive condition affecting about 1 in 10,000 people in the Europe, with a higher rate in some countries, like Ireland and Italy. In Italy, newborn screening (NBS) by MS/MS allows the diagnostic suspicion of PKU and its variants (Hyperphenylalaninemia (HPA), Tetrahydrobiopterin (BH4) synthesis deficiency, and Tetrahydrobiopterin (BH4) recycling deficiency) through the quantification of Phenylalanine (Phe) and the Phenylalanine/Tyrosine (Phe/Tyr) ratio in dried blood Spot (DBS) samples. Here, we report a
case of an HPA whose suspicion was possible with expanded NBS, even if the normal-weight newborn was in total parenteral nutrition (TPN). It is known that TPN may present metabolic alterations, mainly for amino acids at NBS in MS/MS, frequently causing false positives. Actually, TPN is considered a special protocol in NBS, requiring several sample collections. In particular, a DBS sample is required before TPN, at basal time point (48 h after birth) and 72 h after the end of the procedure. In the
case we report, even if the first DBS sample (before TPN) resulted negative, the repeated NBS tests revealed increased levels of Phe and dramatically high Phe/Tyr ratio. Thus, the newborn was recalled, and the NBS test was repeated several times before that HPA suspicion was confirmed by other specific biochemical tests. This
case highlights the importance of Phe/Tyr ratio, only detectable by MS/MS analysis, in supporting the diagnostic suspicion during amino acids administration in the neonatal period.