Schadewaldt Peter, Kamalanathan Loganathan, Hammen Hans Werner, Wendel Udo
Klinik für Allgemeine Pädiatrie, Universitätsklinikum, Heinrich-Heine-Universität Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Mol Genet Metab. 2004 Jan;81(1):31-44. doi: 10.1016/j.ymgme.2003.10.007.
The age dependence of endogenous galactose formation was investigated in Q188R homozygous galactosemic patients (n=18; 4-38 years) using the primed continuous infusion approach with D-[1-13C]galactose as a substrate. Studies were conducted under postabsorptive conditions (fasting >10h) and good metabolic control. In the patients, the release of galactose from endogenous sources into plasma (R(a)) decreased with age and ranged from 4.6 to 2.0 micromol/kg body weight per h. Galactitol and galactonate release rates paralleled the galactose R(a) but at a lower level. The mean relation of galactose, galactitol, and galactonate release was 10:5:1. Statistically, there was a highly significant (p<0.0001) inverse correlation between total galactose release (i.e., sum of R(a) plus galactitol and galactonate release) and age. The data (total galactose=y, age=t) were best fitted to the simple exponential model y=y(0)+axexp(-bt) by non-linear regression analysis. The parameter estimates were y(0)=3.0+/-0.2, a=6.5+/-0.4, and b=0.11+/-0.02. The value of y(0) provides an estimate of total galactose release in adult patients (i.e., approximately 13 mg/kg body weight per day), summation operator (y(0)+a) provides an estimate for galactosemic newborns (i.e., approximately 41 mg/kg body weight per day). The data show that significant amounts of endogenous galactose are formed in galactosemic patients with release rates being several fold higher in infants than in adults. The present findings can explain the persistently elevated galactose-1-phosphate levels in erythrocytes-and its age dependence-in galactosemic patients even when under strict dietary treatment.
采用以D-[1-13C]半乳糖为底物的预充连续输注法，对18例Q188R纯合半乳糖血症患者（年龄4 - 38岁）内源性半乳糖生成的年龄依赖性进行了研究。研究在吸收后状态（禁食>10小时）且代谢控制良好的条件下进行。在这些患者中，内源性半乳糖释放入血浆的速率（R(a)）随年龄增长而降低，范围为每小时4.6至2.0微摩尔/千克体重。半乳糖醇和半乳糖酸的释放速率与半乳糖R(a)平行，但水平较低。半乳糖、半乳糖醇和半乳糖酸释放的平均关系为10:5:1。统计学上，总半乳糖释放量（即R(a)加上半乳糖醇和半乳糖酸释放量之和）与年龄之间存在高度显著的负相关（p<0.0001）。通过非线性回归分析将数据（总半乳糖=y，年龄=t）最佳拟合为简单指数模型y = y(0)+axexp(-bt)。参数估计值为y(0)=3.0±0.2，a = 6.5±0.4，b = 0.11±0.02。y(0)的值提供了成年患者总半乳糖释放量的估计值（即约每天13毫克/千克体重），求和运算符（y(0)+a）提供了半乳糖血症新生儿的估计值（即约每天41毫克/千克体重）。数据表明，半乳糖血症患者体内会形成大量内源性半乳糖，婴儿的释放速率比成年人高几倍。目前的研究结果可以解释即使在严格饮食治疗下，半乳糖血症患者红细胞中半乳糖-1-磷酸水平持续升高及其年龄依赖性的现象。
