N-Acetylcysteine Therapy in an Infant with Transaldolase Deficiency Is Well Tolerated and Associated with Normalization of Alpha Fetoprotein Levels
N-Acetylcysteine Therapy in an Infant with Transaldolase Deficiency Is Well Tolerated and Associated with Normalization of Alpha Fetoprotein Levels
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DOI：
10.1007/8904_2016_555
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Berry, Gerard T.
中科院分区：
文献类型：
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作者：
Rodan, Lance H.;Berry, Gerard T.
转醛醇酶缺乏症是一种罕见的磷酸戊糖途径的常染色体隐性遗传疾病，临床表现为进展为肝硬化、肾病、结缔组织异常（类似皮肤松弛）、凝血病、血细胞减少和肝细胞癌风险增加。在许多情况下，死亡发生在婴儿期或幼儿期。目前还没有针对人类转醛醇酶缺乏症的既定治疗方法。最近在转醛醇酶缺乏的敲除小鼠模型中的工作已经证明了补充谷胱甘肽前体N-乙酰半胱氨酸（NAC）的益处。我们描述了一个婴儿与遗传学证实转醛醇酶缺乏症与多系统参与，包括肝脏肿大和甲胎蛋白显着升高。严格避免使用对乙酰氨基酚。口服NAC治疗6个月耐受性良好，与甲胎蛋白水平持续正常化和稳定的临床病程相关。正常血清甲胎蛋白在该患者中的临床意义尚不确定，尽管其可能反映了小鼠疾病模型中所提示的肝细胞损伤减少和肝癌发生减少。NAC补充剂可为转醛醇酶缺乏症患者提供益处。将需要更长时间的随访和关于转醛醇酶缺乏症患者对NAC补充的反应的数据，以进一步评估疗效和优化剂量。
Transaldolase deficiency is a rare autosomal recessive disorder of the pentose phosphate pathway that presents clinically with infantile-onset hepatopathy progressing to cirrhosis, nephropathy, connective tissue abnormalities resembling cutis laxa, coagulopathy, cytopenias, and increased risk of hepatocellular carcinoma. In many cases, death occurs in infancy or early childhood. There is no established treatment for transaldolase deficiency in humans. Recent work in a knockout mouse model of transaldolase deficiency has demonstrated a benefit to supplementation with the glutathione precursor N-acetylcysteine (NAC). We describe an infant with genetically confirmed transaldolase deficiency with multisystem involvement, including liver enlargement and markedly elevated alpha fetoprotein. Acetaminophen was strictly avoided. Treatment with oral NAC over a 6-month period was well tolerated and was associated with a sustained normalization of alpha fetoprotein levels and stable clinical course. The clinical significance of normalized serum alpha fetoprotein in this patient is not certain, although it may reflect decreased hepatocyte injury and reduced hepatocar-cinogenesis as has been suggested in the mouse disease model. NAC supplementation may provide benefit in humans with transaldolase deficiency. Longer follow-up and data on the response of additional patients with transaldolase deficiency to NAC supplementation will be required to further evaluate efficacy and optimize dosing.