University College Dublin, Clinical Research Centre, Mater Misericordiae University Hospital, Ireland.
Mol Genet Metab. 2012 Feb;105(2):212-20. doi: 10.1016/j.ymgme.2011.10.018. Epub 2011 Nov 7.
N-glycan processing and assembly defects have been demonstrated in untreated and partially treated patients with Classical Galactosaemia. These defects may contribute to the ongoing pathophysiology of this disease. The aim of this study was to develop an informative method of studying differential galactose tolerance levels and diet control in individuals with Galactosaemia, compared to the standard biochemical markers. Ten Galactosaemia adults with normal intellectual outcomes were analyzed in the study. Five subjects followed galactose liberalization, increments of 300 mg to 4000 mg/day over 16 weeks, and were compared to five adult Galactosaemia controls on a galactose restricted diet. All study subjects underwent clinical and biochemical monitoring of red blood cell galactose-1-phosphate (RBC Gal-1-P) and urinary galactitol levels. Serum N-glycans were isolated and analyzed by normal phase high-performance liquid chromatography (NP-HPLC) with galactosylation of IgG used as a specific biomarker of galactose tolerance. IgG N-glycan profiles showed consistent individual alterations in response to diet liberalization. The individual profiles were improved for all, but one study subject, at a galactose intake of 1000 mg/day, with decreases in agalactosylated (G0) and increases in digalactosylated (G2) N-glycans. We conclude that IgG N-glycan profiling is an improved method of monitoring variable galactosylation and determining individual galactose tolerance in Galactosaemia compared to the standard methods.
未经治疗和部分治疗的经典半乳糖血症患者存在 N-糖链加工和组装缺陷。这些缺陷可能导致该疾病的持续病理生理学变化。本研究旨在开发一种信息丰富的方法，以研究半乳糖血症患者的不同半乳糖耐量水平和饮食控制，与标准生化标志物相比。本研究分析了 10 名具有正常智力发育结果的半乳糖血症成年人。5 名受试者遵循半乳糖自由化，在 16 周内每天增加 300mg 至 4000mg，并与 5 名半乳糖血症对照者在半乳糖限制饮食上进行比较。所有研究对象均接受红细胞半乳糖-1-磷酸（RBC Gal-1-P）和尿半乳糖醇水平的临床和生化监测。用 IgG 的半乳糖基化作为半乳糖耐量的特异性生物标志物，通过正相高效液相色谱（NP-HPLC）分离和分析血清 N-糖链。IgG N-糖链图谱显示，在饮食自由化后，所有受试者（除 1 名受试者外）的个体图谱均发生一致改变。在每天摄入 1000mg 半乳糖时，所有受试者（除 1 名受试者外）的非半乳糖化（G0）和双半乳糖化（G2）N-糖链均减少，个体图谱得到改善。我们得出结论，与标准方法相比，IgG N-糖链图谱分析是一种更好的监测半乳糖血症中可变半乳糖化和确定个体半乳糖耐量的方法。
