Brand Kenneth, Landry Daniel, Mulhern Jeffrey, Braden Gregory
UMASS Chan Baystate Medical Center, Springfield, USA.
BMC Nephrol. 2025 Apr 7;26(1):179. doi: 10.1186/s12882-025-04068-5.
Hyperkalemic Periodic Paralysis (hyperPP) is an autosomal dominant genetic disorder where high extracellular potassium is associated with skeletal muscle depolarization and both flaccid muscle weakness as well as delayed muscle relaxation that can lead to myotonia and myopathy. Interventions have typically relied on avoidance of triggers, low potassium diets, and diuretics like acetazolamide and diclofenamide with limited success.
The patient is a 48 year old man with hyperPP from a familial autosomal dominant sodium channel point mutation in the SCN4A gene at position 704 with a Threonine to Methionine substitution that lead to symptoms starting in early childhood. By age 30 he developed permanent muscle weakness and neither acetazolamide nor diclofenamide as interventions had improved his myopathy. In the spring of 2023, semaglutide was initiated for weight loss. Before the semaglutide he could not rise out of a chair without help and his gait was very slow. Over the next year his strength and quality of life returned to levels he had not had in decades.
This is a promising alternative treatment for hyperPP. By directly acting on skeletal muscle both dependent and independent of insulin, Semaglutide and likely other Glucagon-like peptide agonists show promise as a novel once weekly option that may treat not just the hyperkalemic periodic paralysis but also the skeletal muscle atrophy in a multimodal way.
高钾性周期性麻痹（hyperPP）是一种常染色体显性遗传病，细胞外钾离子水平升高与骨骼肌去极化相关，会导致弛缓性肌无力以及肌肉舒张延迟，进而引发肌强直和肌病。治疗方法通常依赖于避免诱因、低钾饮食以及使用乙酰唑胺和双氯芬酰胺等利尿剂，但效果有限。
该患者为一名48岁男性，患有高钾性周期性麻痹，其家族性常染色体显性遗传的SCN4A基因在704位发生点突变，苏氨酸被甲硫氨酸取代，导致症状始于幼儿期。到30岁时，他出现了永久性肌无力，乙酰唑胺和双氯芬酰胺作为治疗手段均未能改善其肌病。2023年春季，开始使用司美格鲁肽进行减肥。在使用司美格鲁肽之前，他在无人帮助的情况下无法从椅子上起身，步态非常缓慢。在接下来的一年里，他的力量和生活质量恢复到了几十年来未曾有过的水平。
这是一种有前景的高钾性周期性麻痹替代治疗方法。司美格鲁肽以及其他可能的胰高血糖素样肽激动剂通过直接作用于骨骼肌，无论是否依赖胰岛素，都显示出有望成为一种新型的每周一次的治疗选择，不仅可以治疗高钾性周期性麻痹，还可以以多模式方式治疗骨骼肌萎缩。
