Thewissen R M J, Post M A, Maas D M, Veizaj R, Wagenaar I, Alsady M, Kools J, Bouman K, Zweers H, Meregalli P G, van der Kooi A J, van Doorn P A, Groothuis J T, Lefeber D J, Voermans N C
Department of Neurology Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center Nijmegen The Netherlands.
Department of Rehabilitation Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center Nijmegen The Netherlands.
JIMD Rep. 2024 Mar 4;65(3):171-181. doi: 10.1002/jmd2.12394. eCollection 2024 May.
Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (), fukutin-related protein (), and fukutin () genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation ( < 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.
三种形式的肌肉营养不良——糖基化肌营养不良症与核糖醇途径有关。这些包括含异戊二烯合酶结构域蛋白（）、福金相关蛋白（）和福金（）基因的突变。上述酶是α-肌营养不良蛋白O-聚糖中核糖醇磷酸键生成所必需的。糖基化肌营养不良症的轻症表现为缓慢进展的肌肉无力，而重症则还累及眼睛和大脑。先前的研究表明，核糖可增加细胞内二磷酸胞苷-核糖醇（CDP-核糖醇）的浓度并具有治疗作用。在此，我们报告了一名因纯合突变导致的2I型肢带型肌营养不良症（LGMD2I）患者在6个月内口服核糖补充剂的安全性和效果。9克或18克/天剂量的核糖耐受性良好。补充18克核糖可使肌酸激酶水平降低70%。此外，代谢组学显示补充18克核糖后CDP-核糖醇水平显著升高（<0.001）。虽然未观察到临床和患者报告的结局指标有客观改善，但患者报告主观上肌肉力量、疲劳和疼痛有所改善。本病例研究表明，糖基化肌营养不良症患者补充核糖是安全的，并突出了未来关于其潜在作用研究的重要性。
