Department of Pediatrics, Medical Academy, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania.
Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania.
Medicina (Kaunas). 2024 Jan 11;60(1):135. doi: 10.3390/medicina60010135.
Hereditary type 1 tyrosinemia (HT1) is a rare inherited autosomal recessive disorder of tyrosine metabolism, characterized by progressive liver damage, dysfunction of kidney tubules, and neurological crises. In the course of this disease, due to the deficiency of the enzyme fumarylacetoacetate hydrolase (FAH), toxic intermediate metabolites of tyrosine breakdown, such as fumarylacetoacetate (FAA), succinylacetoacetate (SAA), and succinylacetone (SA), accumulate in liver and kidney cells, causing cellular damage. Because of this, an increased SA concentration in the blood or urine is pathognomonic of HT1. In the year 2000, HT1 was diagnosed in Lithuania for the first time, and this was the first time when a specific treatment for HT1 was administered in the country. Over two decades, four cases of this disease have been diagnosed in Lithuania. In the first of these patients, the disease was diagnosed in infancy, manifesting as liver damage with liver failure. Treatment with nitisinone was initiated, which continues to be administered, maintaining normal liver function. Liver transplantation was performed on two subsequent patients due to complications of HT1. It is crucial to diagnose HT1 as early as possible in order to reduce or completely eliminate complications related to the disease, including progressive liver failure and kidney dysfunction, among others. This can only be achieved by conducting a universal newborn screening for tyrosinemia and by starting treatment with nitisinone (NTBC) before the age of 1 month in all cases of HT1. However, in those countries where this screening is not being carried out, physicians must be aware of and consider this highly rare disorder. They should be vigilant, paying attention to even minimal changes in a few specific laboratory test results-such as unexplained anemia alongside neutropenia and thrombocytopenia-and should conduct more detailed examinations to determine the causes of these changes. In this article, we present the latest clinical case of HT1 in Lithuania, diagnosed at the Children's Diseases' Clinic of the Lithuanian University of Health Sciences (LUHS) Hospital Kaunas Clinics. The case manifested as life-threatening acute liver failure in early childhood. This article explores and discusses the peculiarities of diagnosing this condition in the absence of universal newborn screening for tyrosinemia in the country, as well as the course, treatment, and ongoing monitoring of patients with this disorder.
遗传性酪氨酸血症 1 型(HT1)是一种罕见的常染色体隐性遗传酪氨酸代谢紊乱疾病,其特征为进行性肝损伤、肾小管功能障碍和神经危象。在该疾病的病程中,由于酶延胡索酰乙酰乙酸水解酶(FAH)的缺乏,酪氨酸分解的有毒中间代谢物,如延胡索酰乙酰乙酸(FAA)、琥珀酰乙酰乙酸(SAA)和琥珀酰丙酮(SA),在肝和肾细胞中积累,导致细胞损伤。正因为如此,血液或尿液中 SA 浓度的增加是 HT1 的特征性表现。2000 年,立陶宛首次诊断出 HT1,这也是该国首次对 HT1 进行特定治疗。在过去的二十多年里,立陶宛共诊断出 4 例该疾病。在这些患者中的第一个患者中,疾病在婴儿期被诊断出来,表现为肝损伤和肝功能衰竭。开始使用尼替西农进行治疗,目前仍在继续使用,以维持正常的肝功能。由于 HT1 的并发症,对随后的两名患者进行了肝移植。早期诊断 HT1 至关重要,以减少或完全消除与疾病相关的并发症,包括进行性肝功能衰竭和肾功能障碍等。只有通过对酪氨酸血症进行普遍的新生儿筛查,并在所有 HT1 病例中在 1 个月龄之前开始使用尼替西农(NTBC)治疗,才能实现这一目标。然而,在那些未进行这种筛查的国家,医生必须意识到并考虑到这种非常罕见的疾病。他们应该保持警惕,注意几个特定实验室检测结果的微小变化,例如原因不明的贫血伴有中性粒细胞减少和血小板减少,并进行更详细的检查以确定这些变化的原因。本文介绍了立陶宛大学健康科学大学医院考纳斯临床儿童疾病诊所最新诊断的 HT1 临床病例。该病例在儿童早期表现为危及生命的急性肝功能衰竭。本文探讨和讨论了在该国未进行普遍新生儿酪氨酸血症筛查的情况下诊断这种疾病的特点,以及该疾病患者的病程、治疗和持续监测。