Verhoeven N M, Wallot M, Huck J H J, Dirsch O, Ballauf A, Neudorf U, Salomons G S, van der Knaap M S, Voit T, Jakobs C
Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2005;28(2):169-79. doi: 10.1007/s10545-005-5261-6.
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 heterogeneous clinical presentation with highly variable severity.
本文描述了第二例被发现患有转醛醇酶（TALDO1；EC 2.2.1.2）缺乏症的患者。临床上，该患者在新生儿期出现了严重肝功能衰竭的多种体征：严重凝血功能障碍、低血清蛋白、血氨升高和低血糖。她有全身性水肿、中度肌肉张力减退和畸形体征。肝脏体积减小，脾脏中度肿大。有严重的心脏肥大。临床病程的特点是难治性肝功能衰竭和进行性心肌肥大。该患儿于18天时死于呼吸衰竭。在尿液中，发现赤藓糖醇、阿糖醇和核糖醇升高，提示转醛醇酶缺乏。对培养的成纤维细胞进行的酶学研究显示未检测到转醛醇酶活性。TALDO1基因的DNA序列分析显示存在纯合错义突变（575G>A），导致第192位氨基酸发生改变（精氨酸变为组氨酸，R192H）。该氨基酸是转醛醇酶蛋白催化位点的一部分。这例患有转醛醇酶缺乏症和肝功能衰竭的第二例患者的发现表明，这种疾病具有异质性临床表现，严重程度差异很大。
