Ambrose Anastasia, McCabe Morganne, Hung Clara, Sosova Iveta, Seres Peter, Mercimek-Andrews Saadet
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Alberta Newborn Screening and Biochemical Genetics Laboratory, University of Alberta Hospital, Alberta Precision Laboratories, Edmonton, Alberta, Canada.
Mol Genet Metab Rep. 2025 Apr 3;43:101212. doi: 10.1016/j.ymgmr.2025.101212. eCollection 2025 Jun.
Biallelic pathogenic variants in result in phosphoglucomutase 1 (PGM1) deficiency that is one of the congenital disorders of glycosylation (CDG) (PGM1-CDG). Phenotypic spectrum includes congenital malformations, and muscular, cardiac, hepatic, endocrine and hematologic phenotypes. Current treatment consists of D-galactose therapy that results in clinical and biochemical improvements. To improve fatigue, and exercise intolerance, we started creatine supplementation therapy.
We reviewed electronic patient chart. We applied Nijmegen Pediatric CDG Rating Scale (NPCRS) and The Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F). We measured creatine metabolism biomarkers.
This is a 29-year-old female with PGM1-CDG, confirmed diagnosis by clinical exome sequencing. She has been treated with D-galactose therapy which did not improve her fatigue and exercise intolerance. She was started on creatine supplementation therapy at the age of 27 years which led to decreased daytime sleeping, increased exercise capacity and improvements in her NPCRS, and FACIT-F. Her plasma guanidinoacetate was low. She had elevated urine galactitol on D-galactose therapy.
PGM1-CDG associated myopathy is likely due to combination of several factors including abnormal muscle carbohydrate metabolism, abnormal N-glycosylation of proteins involved in the muscle functions and creatine transport and altered muscle energy homeostasis. It was previously shown that creatine supplementation therapy improves myopathy in patients with mitochondrial cytopathies. We think that the use of creatine supplementation therapy coincided with improvements in fatigue and exercise intolerance subjectively and objectively in our patient.
双等位基因致病性变异导致磷酸葡萄糖变位酶1（PGM1）缺乏，这是一种先天性糖基化障碍（CDG）（PGM1-CDG）。表型谱包括先天性畸形以及肌肉、心脏、肝脏、内分泌和血液学表型。目前的治疗方法是D-半乳糖疗法，可带来临床和生化改善。为改善疲劳和运动不耐受，我们开始了肌酸补充疗法。
我们查阅了电子病历。我们应用了奈梅亨儿科CDG评分量表（NPCRS）和慢性病治疗功能评估疲劳量表（FACIT-F）。我们测量了肌酸代谢生物标志物。
这是一名29岁的PGM1-CDG女性患者，通过临床外显子测序确诊。她接受了D-半乳糖疗法，但疲劳和运动不耐受并未改善。她在27岁时开始接受肌酸补充疗法，这导致白天睡眠时间减少、运动能力增强，并且她的NPCRS和FACIT-F有所改善。她血浆中的胍基乙酸水平较低。在接受D-半乳糖疗法时，她尿中的半乳糖醇水平升高。
PGM1-CDG相关的肌病可能是由于多种因素共同作用所致，包括异常的肌肉碳水化合物代谢、参与肌肉功能和肌酸转运的蛋白质的异常N-糖基化以及肌肉能量稳态的改变。先前的研究表明，肌酸补充疗法可改善线粒体细胞病患者的肌病。我们认为，在我们的患者中，肌酸补充疗法的使用与主观和客观上疲劳和运动不耐受的改善同时出现。
