A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency
A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency
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DOI：
10.1007/s10545-005-5261-6
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Jakobs, C
中科院分区：
文献类型：
--
作者：
Verhoeven, NM;Wallot, M;Jakobs, C
本文描述了第二例发现患有转醛醇酶缺乏症（TALDO 1; EC 2.2.1.2）的患者。临床上，该患者在新生儿期出现重度肝功能衰竭的几种体征：重度凝血病、低血清蛋白、血氨升高和低血糖。她有全身水肿、中度肌张力减退和畸形体征。肝脏缩小，脾脏中度增大。有严重的心脏肥大。临床过程的特点是顽固性肝衰竭和进行性心肌肥厚。这名儿童在18天时死于呼吸衰竭。在尿液中，发现了β-淀粉酶、阿拉伯糖醇和核糖醇的升高，表明转醛醇酶缺乏。在培养的成纤维细胞中的酶研究显示不可检测的转醛醇酶活性。TALDO 1基因的DNA序列分析显示纯合错义突变（575 G A），导致192位氨基酸改变（精氨酸变为组氨酸，R192 H）。该氨基酸是转醛醇酶蛋白催化位点的一部分。发现第二例患者患有转醛醇酶缺乏症和肝功能衰竭，表明这种疾病具有高度可变的严重程度的异质性临床表现。
This paper describes the second patient found to be affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Clinically, this patient presented in the neonatal period with several signs of severe liver failure: severe coagulopathy, low serum protein, elevated blood ammonia, and hypoglycaemia. She had generalized oedema, moderate muscular hypotonia, and dysmorphic signs. Liver size was decreased, and the spleen was moderately enlarged. There was severe cardiomegaly. The clinical course was characterized by intractable liver failure and progressive myocardial hypertrophy. The child died at the age of 18 days from respiratory failure. In urine, elevations of erythritol, arabitol and ribitol were found, suggesting a deficiency of transaldolase. Enzyme studies in cultured fibroblasts showed undetectable transaldolase activity. DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G> A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H). This amino acid is part of the catalytic site of the transaldolase protein. Discovery of this second patient affected with transaldolase deficiency and liver failure suggests that this disorder has a heterogenous clinical presentation with highly variable severity.