Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG.
Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG.
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DOI：
10.1016/j.ymgme.2014.06.002
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发表时间：
2014-08
影响因子：
3.8
通讯作者：
Morava, Eva
中科院分区：
文献类型：
--
作者：
Morava, Eva
我们最近重新定义了磷酸葡萄糖糖化酶-1缺乏症不仅是一种参与正常糖原代谢的酶缺陷，而且是一种先天性的蛋白质糖基化错误。磷酸葡萄糖糖化酶-1是糖酵解和糖生成的关键酶，它催化磷酸在葡萄糖上从1位向6位的双向转移。葡萄糖-1- p和udp -葡萄糖与半乳糖代谢密切相关。正常的PGM1活性对于空腹期间有效的糖酵解非常重要。活性葡萄糖和半乳糖是正常蛋白糖基化所必需的。涉及活性糖浓度异常的复杂缺陷导致低血糖和两种主要的表型表现，一种是原发性肌肉受累，另一种是严重的多系统疾病。多系统表型包括生长迟缓和畸形，如腭裂或小舌，以及肝脏、内分泌和可能的心肌病。患者智力正常。转铁蛋白半乳糖基化降低是质谱分析的一个特征发现。先前对患者成纤维细胞的体外研究表明，半乳糖补充剂可改善糖基化。4例PGM1缺乏症患者已接受d -半乳糖（同情使用）的试验，结果显示血清转铁蛋白低糖基化得到改善。肝功能、内分泌异常和低血糖发作频率均有改善。没有观察到副作用。补充半乳糖似乎不能解决所有的临床症状。添加复合碳水化合物显示了额外的临床改善。根据现有的临床数据，我们建议在PGM1-CDG中考虑使用0.5-1g /kg/天的d -半乳糖和最大50g/天的口服半乳糖治疗。关于半乳糖治疗的现有数据必须被视为初步观察。一项前瞻性多中心试验正在进行中，以评估半乳糖补充剂的功效和最佳d -半乳糖剂量。
We recently redefined phosphoglucomutase-1 deficiency not only as an enzyme defect, involved in normal glycogen metabolism, but also an inborn error of protein glycosylation. Phosphoglucomutase-1 is a key enzyme in glycolysis and glycogenesis by catalyzing in the bidirectional transfer of phosphate from position 1 to 6 on glucose. Glucose-1-P and UDP-glucose are closely linked to galactose metabolism. Normal PGM1 activity is important for effective glycolysis during fasting. Activated glucose and galactose are essential for normal protein glycosylation. The complex defect involving abnormal concentrations of activated sugars leads to hypoglycemia and two major phenotypic presentations, one with primary muscle involvement and the other with severe multisystem disease. The multisystem phenotype includes growth delay and malformations, like cleft palate or uvula, and liver, endocrine and possible cardiomyopathy. The patients have normal intelligence. Decreased transferrin galactosylation is a characteristic finding on mass spectrometry. Previous in vitro studies in patient fibroblasts showed an improvement of glycosylation on galactose supplements. Four patients with PGM1 deficiency have been trialed on D-galactose (compassionate use), and showed improvement of serum transferrin hypoglycosylation. There was a parallel improvement of liver function, endocrine abnormalities and a decrease in the frequency of hypoglycemic episodes. No side effects have been observed. Galactose supplementation didn't seem to resolve all clinical symptoms. Adding complex carbohydrates showed an additional clinical amelioration. Based on the available clinical data we suggest to consider the use of 0.5–1g/kg/day D-galactose and maximum 50g/day oral galactose therapy in PGM1-CDG. The existing data on galactose therapy have to be viewed as preliminary observations. A prospective multicenter trial is ongoing to evaluate the efficacy and optimal D-galactose dose of galactose supplementation.
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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：
3.9
作者：
BIRLOUEZARAGON, I;ALLOUSSI, S
通讯作者：
ALLOUSSI, S
影响因子：
3.6
作者：
Mandato, C;Brive, LE;Vajro, P
通讯作者：
Vajro, P
影响因子：
5.8
作者：
Preisler, Nicolai;Laforet, Pascal;Vissing, John
通讯作者：
Vissing, John
影响因子：
3.9
作者：
RAY, WJ;MILDVAN, AS;GRUTZNER, JB
通讯作者：
GRUTZNER, JB