PDF(Pubmed)
Abstract：
Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism that leads to severe liver, kidney, and neurological dysfunction. Newborn screening (NBS) can enable a timely diagnosis and early initiation of treatment. We presented the follow up of the only two Slovenian patients diagnosed with HT1. Metabolic control was monitored by measuring tyrosine, phenylalanine and succinylacetone from dried blood spots (DBSs). Retrograde screening of HT1 was performed from DBSs taken at birth using tandem mass spectrometry. First patient was diagnosed at the age of 6 months in the asymptomatic phase due to an abnormal liver echogenicity, the other presented at 2.5 months with an acute liver failure and needed a liver transplantation. The first was a compound heterozygote for a novel FAH intronic variant c.607-21A>G and c.192G>T whereas the second was homozygous for c.192G>T. At the non-transplanted patient, 66% of tyrosine and 79% of phenylalanine measurements were in strict reference ranges of 200-400 μmol/L and >30 μmol/L, respectively, which resulted in a favorable cognitive outcome at 3.6 years. On retrograde screening, both patients had elevated SA levels; on the other hand, tyrosine was elevated only at one. We showed that non-coding regions should be analyzed when clinical and biochemical markers are characteristic of HT1. DBSs represent a convenient sample type for frequent amino acid monitoring. Retrograde diagnosis of HT1 was possible after more than three years of birth with SA as a primary marker, complemented by tyrosine.
摘要：
酪氨酸血症1型（HT1）是酪氨酸分解代谢的先天性错误，导致严重的肝脏，肾,和神经功能障碍。新生儿筛查（NBS）可以及时诊断并尽早开始治疗。我们介绍了仅有的两名诊断为HT1的斯洛文尼亚患者的随访情况。通过测量酪氨酸来监测代谢控制，苯丙氨酸和琥珀酰丙酮从干燥的血斑（DBSs）。使用串联质谱法从出生时采集的DBS中进行HT1的逆行筛查。由于肝脏回声异常，第一例患者在无症状期被诊断为6个月大，另一例在2.5个月时出现急性肝功能衰竭,需要进行肝移植.第一个是新型FAH内含子变体c.607-21A>G和c.192G>T的复合杂合子，而第二个是c.192G>T的纯合。在非移植患者身上，66％的酪氨酸和79％的苯丙氨酸测量值在200-400μmol/L和>30μmol/L的严格参考范围内，分别,这导致了一个良好的认知结果在3.6年。在逆行筛查中，两名患者的SA水平均升高；另一方面，酪氨酸仅在1时升高。我们表明，当临床和生化标志物具有HT1的特征时，应分析非编码区。DBS代表用于频繁氨基酸监测的方便的样品类型。在以SA为主要标志物的三年多出生后，HT1的逆行诊断是可能的。辅以酪氨酸。
