Pekrun A, Neubauer B A, Eber S W, Lakomek M, Seidel H, Schröter W
Universitäts-Kinderklinik, Göttingen, Germany.
Clin Genet. 1995 Apr;47(4):175-9. doi: 10.1111/j.1399-0004.1995.tb03955.x.
Inherited deficiency of the glycolytic enzyme triosephosphate isomerase leads to a multisystem disorder characterized by progressive neuromuscular dysfunction, chronic nonspherocytic hemolytic anemia and increased susceptibility to severe infections. Most patients die within the first 6 years. We examined a family with severe triosephosphate isomerase deficiency. The 1-year-old index patient suffered from hemolytic anemia, neuromuscular impairment and pneumonias, with the necessity of intermitten mechanical ventilation. Triosephosphate isomerase activity in erythrocytes was reduced to about 20% of normal. Heat stability of the enzyme was strongly reduced; concentration of the physiological substrate, dihydroxyacetone phosphate was increased 20-fold due to the metabolic block. Direct sequencing of the triosephosphate isomerase gene revealed homozygosity for the formerly described GAG-->GAC-mutation changing 104 Glu-->Asp. During a 2nd pregnancy we examined a cord blood sample obtained in the 19th gestational week. The biochemical data on enzyme activity, heat stability of the enzyme and concentration of dihydroxyacetone phosphate were in the normal range. The molecular genetic analysis confirmed the presence of the normal triosephosphate isomerase alleles. Pregnancy was continued, resulting in the delivery of an unaffected, healthy newborn.
糖酵解酶磷酸丙糖异构酶的遗传性缺陷会导致一种多系统疾病，其特征为进行性神经肌肉功能障碍、慢性非球形红细胞溶血性贫血以及对严重感染的易感性增加。大多数患者在6岁前死亡。我们研究了一个患有严重磷酸丙糖异构酶缺乏症的家庭。1岁的索引患者患有溶血性贫血、神经肌肉损伤和肺炎，需要间歇性机械通气。红细胞中磷酸丙糖异构酶的活性降至正常水平的约20%。该酶的热稳定性大幅降低；由于代谢阻滞，生理底物磷酸二羟丙酮的浓度增加了20倍。对磷酸丙糖异构酶基因进行直接测序，发现其为先前描述的GAG→GAC突变的纯合子，该突变使104位谷氨酸变为天冬氨酸。在第二次怀孕期间，我们检测了孕19周时采集的脐带血样本。关于酶活性、酶热稳定性和磷酸二羟丙酮浓度的生化数据均在正常范围内。分子遗传学分析证实存在正常的磷酸丙糖异构酶等位基因。继续妊娠，最终分娩出一名未受影响的健康新生儿。
