Limitations of galactose therapy in phosphoglucomutase 1 deficiency.
Limitations of galactose therapy in phosphoglucomutase 1 deficiency.
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DOI：
10.1016/j.ymgmr.2017.07.010
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发表时间：
2017-12
影响因子：
1.9
通讯作者：
Marquardt T
中科院分区：
文献类型：
--
作者：
Nolting K;Park JH;Tegtmeyer LC;Zühlsdorf A;Grüneberg M;Rust S;Reunert J;Du Chesne I;Debus V;Schulze-Bahr E;Baxter RC;Wada Y;Thiel C;van Schaftingen E;Fingerhut R;Marquardt T
磷酸葡萄糖变位酶 1 缺乏症（PGM1 缺乏症）已被确定为糖原增多症和先天性糖基化障碍 (CDG)。表型包括肝病、肌病、口咽畸形、心脏病和生长迟缓。每天每公斤体重 1 克的口服半乳糖补充剂被认为是首选疗法。我们报告了一位患有导致突变的新疾病的患者，该患者接受了 1.5 年的口服半乳糖补充剂治疗。最初，升高的转氨酶减少，血清转铁蛋白的蛋白质糖基化迅速改善。然而，长期监测表明，以标准剂量补充半乳糖存在局限性：每天每公斤体重 1 克并不能实现蛋白质糖基化的永久纠正。即使将剂量增加至每公斤体重 2.5 克，也不会导致完全正常化。此外，我们首次描述了心律异常，即与糖基化障碍相关的长 QT 综合征。 IGFBP3 被认为在与 PGM1 缺乏相关的生长迟缓中起主要作用，其质谱分析显示没有糖基化异常。补充半乳糖后生长率没有提高。我们的研究结果表明，目前半乳糖的标准剂量可能太低，无法在所有患者中实现正常的糖基化。此外，PGM1 缺乏导致的生长迟缓是复杂的、多因素的。此外，在治疗 PGM1 缺乏症患者时必须考虑心律异常。
Phosphoglucomutase 1 deficiency (PGM1 deficiency) has been identified as both, glycogenosis and congenital disorder of glycosylation (CDG). The phenotype includes hepatopathy, myopathy, oropharyngeal malformations, heart disease and growth retardation. Oral galactose supplementation at a dosage of 1 g per kg body weight per day is regarded as the therapy of choice. We report on a patient with a novel disease causing mutation, who was treated for 1.5 years with oral galactose supplementation. Initially, elevated transaminases were reduced and protein glycosylation of serum transferrin improved rapidly. Long-term surveillance however indicated limitations of galactose supplementation at the standard dose: 1 g per kg body weight per day did not achieve permanent correction of protein glycosylation. Even increased doses of up to 2.5 g per kg body weight did not result in complete normalization. Furthermore, we described for the first time heart rhythm abnormalities, i.e. long QT Syndrome associated with a glycosylation disorder. Mass spectrometry of IGFBP3, which was assumed to play a major role in growth retardation associated with PGM1 deficiency, revealed no glycosylation abnormalities. Growth rate did not improve under galactose supplementation. The results of our study indicate that the current standard dose of galactose might be too low to achieve normal glycosylation in all patients. In addition, growth retardation in PGM1 deficiency is complex and multifactorial. Furthermore, heart rhythm abnormalities must be considered when treating patients with PGM1 deficiency.
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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：
4.6
作者：
Lai, Kent;Elsas, Louis J.;Wierenga, Klaas J.
通讯作者：
Wierenga, Klaas J.
影响因子：
7.4
作者：
Wada, Y;Tajiri, M;Yoshida, S
通讯作者：
Yoshida, S
影响因子：
4
作者：
Firth, SM;Baxter, RC
通讯作者：
Baxter, RC
影响因子：
9.8
作者：
Park, Julien H.;Hogrebe, Max;Marquardt, Thorsten
通讯作者：
Marquardt, Thorsten