Morrow Geneviève, Tanguay Robert M
Laboratoire de génétique cellulaire et développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, Institut de biologie intégrative et des systèmes (IBIS) and PROTEO, Université Laval, 1030 avenue de la médecine, Québec, QC, G1V 0A6, Canada.
Adv Exp Med Biol. 2017;959:9-21. doi: 10.1007/978-3-319-55780-9_2.
Inborn errors of metabolism (IEMs) are a group of diseases involving a genetic defect that alters a metabolic pathway and that presents usually during infancy. The tyrosine degradation pathway contains five enzymes, four of which being associated with IEMs. The most severe metabolic disorder associated with this catabolic pathway is hereditary tyrosinemia type 1 (HT1; OMIM 276700). HT1 is an autosomal recessive disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH), the last enzyme of the tyrosine catabolic pathway. Although a rare disease worldwide, HT1 shows higher incidence in certain populations due to founder effects. The acute form of the disease is characterized by an early onset and severe liver failure while the chronic form appears later and also involves renal dysfunctions. Until 1992 the only treatment for this disease was liver transplantation. Since then, NTBC/Nitisone (a drug blocking the pathway upstream of FAH) is successfully used in combination with a diet low in tyrosine and phenylalanine, but patients are still at risk of developing hepatocellular carcinoma. This chapter summarizes the biochemical and clinical features of HT1.
先天性代谢缺陷（IEMs）是一组涉及遗传缺陷的疾病，该缺陷会改变代谢途径，通常在婴儿期出现。酪氨酸降解途径包含五种酶，其中四种与IEMs有关。与该分解代谢途径相关的最严重的代谢紊乱是1型遗传性酪氨酸血症（HT1；OMIM 276700）。HT1是一种常染色体隐性疾病，由酪氨酸分解代谢途径的最后一种酶——延胡索酰乙酰乙酸水解酶（FAH）缺乏引起。尽管HT1在全球范围内是一种罕见疾病，但由于奠基者效应，在某些人群中发病率较高。该疾病的急性形式的特征是发病早且严重肝功能衰竭，而慢性形式出现较晚，还涉及肾功能障碍。直到1992年，该疾病的唯一治疗方法是肝移植。从那时起，NTBC/尼替西农（一种阻断FAH上游途径的药物）与低酪氨酸和苯丙氨酸饮食联合成功应用，但患者仍有患肝细胞癌的风险。本章总结了HT1的生化和临床特征。
