Anakura M
Hokkaido Igaku Zasshi. 1981 Jan;56(1):1-15.
This study was performed to investigate 1) technical modification of Guthrie method for mass screening to detect histidinemia, 2) patients with histidinemia in view of genetic and biochemical aspects, and 3) therapy of histidinemia in newborn infants. Guthrie method was the useful method for mass screening of histidinemia in newborn infants. It is possible to measure blood level of histidine using by Subutilis spore ATTCC 6633 instead of ATCC 6051. Mass screening of histidinemia was done in about 20,000 newborn infants in Hokkaido, and one case of histidinemia, which was first case in Japan found by this method, was observed. In a case of 5 year-old boy with clinical histidinemia, in whom serum histidine level was 12.1 mg/kl, histidase activity of stratum corneum was not detectable, FIGLU and urocanic acid in urine and urocanic acid in sweat were not detected, the half life of histidine at intravenous histidine loading test was too long to measure. But in other case of 13 year-old boy without clinical signs of histidinemia, elder brother of former case, serum histidine level was 4.7 mg/dl, histidase activity was 11% of normal control, excretion of FIGLU and urocanic acid in urine, and urocanic acid in sweat were observed, and the half life of histidine was 5 hours and 50 minutes (normal: 2 hours and 20 minutes). In both cases, Tryptophan absorption and metabolism were not influenced by high level of blood histidine. Therapy with low histidine milk was made in 3 cases of affected infants. When histidine was given orally in dose of 30-35 mg/kg/day, serum histidine level was down to 3-5 mg/dl in a week in all cases, but in one case low proteinemia an anemia were observed. When histidine was orally given in a dose of 40-50 mg/kg/day, serum histidine level was well controlled. In all cases with histidine limited diets, mental retardation and growth retardation were not found.
1）用于大规模筛查以检测组氨酸血症的格思里方法的技术改进；2）从遗传和生化方面研究组氨酸血症患者；3）新生儿组氨酸血症的治疗。格思里方法是用于新生儿组氨酸血症大规模筛查的有效方法。使用枯草芽孢杆菌孢子ATTCC 6633代替ATCC 6051可以测量血液中的组氨酸水平。在北海道对约20000名新生儿进行了组氨酸血症的大规模筛查，观察到1例组氨酸血症病例，这是通过该方法在日本发现的首例病例。在1例临床诊断为组氨酸血症的5岁男孩中，血清组氨酸水平为12.1mg/kl，角质层的组氨酸酶活性未检测到，尿液中的亚胺甲基谷氨酸和尿刊酸以及汗液中的尿刊酸均未检测到，静脉注射组氨酸负荷试验中组氨酸的半衰期太长无法测量。但在另1例无组氨酸血症临床症状的13岁男孩中，即前1例的哥哥，血清组氨酸水平为4.7mg/dl，组氨酸酶活性为正常对照的11%，观察到尿液中的亚胺甲基谷氨酸和尿刊酸以及汗液中的尿刊酸排泄，组氨酸的半衰期为5小时50分钟（正常：2小时20分钟）。在这两个病例中，色氨酸的吸收和代谢均未受到高血组氨酸水平的影响。对3例患病婴儿采用低组氨酸牛奶进行治疗。当以30 - 35mg/kg/天的剂量口服组氨酸时，所有病例在一周内血清组氨酸水平降至3 - 5mg/dl，但有1例出现低蛋白血症和贫血。当以40 - 50mg/kg/天的剂量口服组氨酸时，血清组氨酸水平得到良好控制。在所有采用组氨酸限制饮食的病例中，均未发现智力发育迟缓或生长发育迟缓。
