Oral D-galactose supplementation in PGM1-CDG.
Oral D-galactose supplementation in PGM1-CDG.
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DOI：
10.1038/gim.2017.41
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Morava E
中科院分区：
文献类型：
--
作者：
Wong SY;Gadomski T;van Scherpenzeel M;Honzik T;Hansikova H;Holmefjord KSB;Mork M;Bowling F;Sykut-Cegielska J;Koch D;Hertecant J;Preston G;Jaeken J;Peeters N;Perez S;Nguyen DD;Crivelly K;Emmerzaal T;Gibson KM;Raymond K;Abu Bakar N;Foulquier F;Poschet G;Ackermann AM;He M;Lefeber DJ;Thiel C;Kozicz T;Morava E
磷酸葡萄糖变位酶-1缺乏症是先天性糖基化障碍（PGM 1-CDG）的一种亚型。既往接受口服D-半乳糖（D-gal）治疗的PGM 1-CDG患者的病例报告显示临床改善。到目前为止，还没有系统的体外和临床研究评估D-半乳糖补充剂的安全性和益处。在一项前瞻性初步研究中，我们评估了9名患者口服D-半乳糖的效果。在18周内，以三次增量将D-半乳糖补充增加至1.5 g/kg/天（最大50 g/天）。在治疗前和治疗期间进行实验室研究，以监测安全性和对血清转铁蛋白糖基化、凝血、肝脏和内分泌功能的影响。此外，在体外表征了D-gal对细胞糖基化的影响。8例患者依从D-gal补充。未报告不良反应。使用1 g/kg/天D-gal后，异常基线结果（ALT/AST/aPTT）已得到改善或正常化。抗凝血酶-III水平和转铁蛋白-糖基化显示出显著改善，半乳糖基化和全聚糖含量增加。治疗前的体外研究显示，患者成纤维细胞中存在N-聚糖低唾液酸化、O-连接聚糖改变、异常LLO特征和异常核苷酸-糖。大多数细胞异常在D-gal治疗后得到改善或正常化。D-gal增加了UDP-Glc和UDP-gal水平，并改善了LLO分数，这与PGM 1-CDG中糖基化的改善一致。在这项初步研究中，口服D-半乳糖补充剂是一种安全有效的PGM 1-CDG治疗方法。转铁蛋白糖基化和ATIII水平是有用的试验终点。目前正在进行更大规模、持续时间更长的审判。
Phosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous case-reports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical improvement. So far no systematic in vitro and clinical studies assessed safety and benefits of D-gal supplementation. In a prospective pilot study, we evaluated the effects of oral D-gal in nine patients. D-gal supplementation was increased to 1.5 g/kg/day (maximum 50 g/day) in three increments over 18 weeks. Laboratory studies were performed before and during treatment to monitor safety and effect on serum transferrin-glycosylation, coagulation, liver and endocrine function. Additionally, the effect of D-gal on cellular glycosylation was characterized in vitro. Eight patients were compliant with D-gal supplementation. No adverse effects were reported. Abnormal baseline results (ALT/AST/aPTT) improved or normalized already using 1g/kg/day D-gal. Antithrombin-III levels and Transferrin-glycosylation showed significant improvement, and increase in galactosylation and whole glycan content. In vitro studies before treatment showed N-glycan hyposialylation, altered O-linked glycans, abnormal LLO-profile, and abnormal nucleotide-sugars in patient fibroblasts. Most cellular abnormalities improved or normalized following D-gal treatment. D-gal increased both UDP-Glc and UDP-gal levels and improved LLO fractions in concert with improved glycosylation in PGM1-CDG. Oral D-gal supplementation is a safe and effective treatment for PGM1-CDG in this pilot study. Transferrin glycosylation and ATIII levels were useful trial end points. Larger, longer duration trials are ongoing.
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DOI：
10.1056/nejmoa1206605
发表时间：
2014-02-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tegtmeyer LC;Rust S;van Scherpenzeel M;Ng BG;Losfeld ME;Timal S;Raymond K;He P;Ichikawa M;Veltman J;Huijben K;Shin YS;Sharma V;Adamowicz M;Lammens M;Reunert J;Witten A;Schrapers E;Matthijs G;Jaeken J;Rymen D;Stojkovic T;Laforêt P;Petit F;Aumaître O;Czarnowska E;Piraud M;Podskarbi T;Stanley CA;Matalon R;Burda P;Seyyedi S;Debus V;Socha P;Sykut-Cegielska J;van Spronsen F;de Meirleir L;Vajro P;DeClue T;Ficicioglu C;Wada Y;Wevers RA;Vanderschaeghe D;Callewaert N;Fingerhut R;van Schaftingen E;Freeze HH;Morava E;Lefeber DJ;Marquardt T
通讯作者：
Marquardt T
影响因子：
15.9
作者：
Niehues, R;Hasilik, M;Marquardt, T
通讯作者：
Marquardt, T
影响因子：
5.1
作者：
Wong, Sunnie Yan-Wai;Beamer, Lesa J.;Morava, Eva
通讯作者：
Morava, Eva
影响因子：
4.2
作者：
Scott, Kyle;Gadomski, Therese;Kozicz, Tamas;Morava, Eva
通讯作者：
Morava, Eva
影响因子：
2.9
作者：
Xia, Baoyun;Zhang, Wenyue;He, Miao
通讯作者：
He, Miao