PDF(Pubmed)
Abstract：
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by a defect in fumarylacetoacetate hydroxylase (FAH) encoded by the FAH gene. Patients with HT1 disorder present with increased blood tyrosine, succinyl acetoacetate, and succinyl acetone levels, and develop clinical manifestations including liver failure, kidney tubular dysfunction, growth failure, rickets, pseudo-porphyric crises, and hepatocellular carcinoma. We encountered two siblings with HT1. Among the siblings, the elder brother developed acute liver failure with coagulopathy at the age of 2 months and was rescued by liver transplantation (LT) following combination therapy with continuous hemodiafiltration and plasma exchange. The younger sister was followed up from the prenatal period for signs of HT1 due to prior history of the condition in her sibling. She was initially considered a carrier of HT1 owing to the lack of overt signs of the disease and negative urine screening for succinyl acetone (SA). She was eventually diagnosed with HT1 because of liver disorder at 9 months of age, associated with a positive urine SA result. Her disease state was controlled by treatment with nitisinone (NTBC). DNA analysis of both siblings identified heterozygous status for a previously reported FAH pathogenic allele (c.782C > T) and a novel likely pathogenic variant (c.688C.G). The siblings have stable lives with no developmental delay or impaired growth. NTBC treatment is effective in preventing the progression of liver and kidney diseases. However, even in cases treated without LT, clinicians should follow up the clinical outcomes over long term, as patients may require LT when developing complications, such as hepatocellular carcinoma.
摘要：
遗传性酪氨酸血症1型（HT1）是由FAH基因编码的富马酸乙酰乙酸羟化酶（FAH）缺陷引起的常染色体隐性遗传疾病。HT1障碍患者出现血酪氨酸升高，乙酰乙酸琥珀酰,和琥珀酰丙酮水平，并发展出包括肝功能衰竭在内的临床表现，肾小管功能障碍，生长失败，病,伪斑状危机，和肝细胞癌。我们遇到了两个有HT1的兄弟姐妹。在兄弟姐妹中，哥哥在2个月大的时候出现了急性肝功能衰竭伴凝血病,并在连续血液透析滤过和血浆置换联合治疗后通过肝移植(LT)抢救.由于其兄弟姐妹的先前病史，从产前开始对妹妹进行HT1迹象的随访。由于缺乏明显的疾病迹象和琥珀酰丙酮（SA）的尿液筛查阴性，她最初被认为是HT1的携带者。她最终在9个月大时因肝脏疾病被诊断出患有HT1，与尿SA阳性结果相关。她的病情通过尼替辛酮（NTBC）治疗得到控制。对两个兄弟姐妹的DNA分析确定了先前报道的FAH致病性等位基因的杂合状态（c.782C>T）和一种新的可能的致病性变体（c.688C。G).兄弟姐妹生活稳定，没有发育迟缓或生长受损。NTBC治疗可有效预防肝脏和肾脏疾病的进展。然而,即使在没有LT治疗的情况下，临床医生应该长期随访临床结果，因为患者在出现并发症时可能需要LT，如肝细胞癌。
