A case report of two siblings with hypertyrosinemia type 1 presenting with hepatic disease with different onset time and severity.
A case report of two siblings with hypertyrosinemia type 1 presenting with hepatic disease with different onset time and severity.
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DOI：
10.1016/j.ymgmr.2022.100892
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发表时间：
2022-09
影响因子：
1.9
通讯作者：
Nakamura, Kimitoshi
中科院分区：
文献类型：
--
作者：
Kawabata, Kazuo;Kido, Jun;Yoshida, Takanobu;Matsumoto, Shirou;Nakamura, Kimitoshi
遗传性酪氨酸血症1型（HT1）是由富马酰乙酸羟化酶（FAH）基因编码的缺陷引起的常染色体隐性遗传病。HT1患者血中酪氨酸、乙酰乙酸琥珀酰、丙酮琥珀酰水平升高，临床表现为肝功能衰竭、肾小管功能障碍、生长衰竭、佝偻病、伪卟啉危象、肝细胞癌等。我们遇到了HT1的两个兄弟。在兄弟姐妹中，哥哥在2个月大时出现急性肝功能衰竭并凝血功能障碍，在持续血液滤过和血浆置换联合治疗后通过肝移植（LT）获救。由于其兄弟姐妹既往有HT1病史，从产前开始对妹妹进行随访，以寻找HT1的迹象。由于缺乏明显的疾病体征，且尿中琥珀酰丙酮（SA）筛查呈阴性，患者最初被认为是HT1携带者。她最终在9个月大时被诊断为HT1，因为肝脏疾病，并伴有尿SA阳性结果。采用尼替西酮（NTBC）治疗，病情得到控制。对两个兄弟姐妹的DNA分析发现了先前报道的FAH致病等位基因（c.782C > T）和一种新的可能致病变异（c.688C.G）的杂合状态。兄弟姐妹生活稳定，没有发育迟缓或生长受损。NTBC治疗在预防肝脏和肾脏疾病进展方面是有效的。然而，即使在不进行肝移植治疗的病例中，临床医生也应该长期随访临床结果，因为患者在出现并发症（如肝细胞癌）时可能需要肝移植。
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.
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DOI：
10.1038/gim.2017.101
发表时间：
2017-12-01
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Chinsky, Jeffrey M;Singh, Rani;Scott, C Ronald
通讯作者：
Scott, C Ronald
影响因子：
3.3
作者：
Daly, A.;Gokmen-Ozel, H.;McKiernan, P.
通讯作者：
McKiernan, P.
影响因子：
1.3
作者：
Karaca, Can A.;Yilmaz, Cahit;Kilic, Murat
通讯作者：
Kilic, Murat
影响因子：
4.2
作者：
Thimm, Eva;Richter-Werkle, Renate;Spiekerkoetter, Ute
通讯作者：
Spiekerkoetter, Ute
与健康对照组相比，酪氨酸血症1型患者的神经认知结果。
影响因子：
3.7
作者：
van Ginkel WG;Jahja R;Huijbregts SC;Daly A;MacDonald A;De Laet C;Cassiman D;Eyskens F;Körver-Keularts IM;Goyens PJ;McKiernan PJ;van Spronsen FJ
通讯作者：
van Spronsen FJ