Xu Jiao-Jiao, Chen Yu-Lan, Yu Hao, Chen Dian-Fu, Li Hong-Fu, Wu Zhi-Ying
Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation Hangzhou, Zhejiang, China.
Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation Hangzhou, Zhejiang, China; Nanhu Brain-Computer Interface Institute, Hangzhou, Zhejiang, China.
Pediatr Neurol. 2025 Sep;170:31-37. doi: 10.1016/j.pediatrneurol.2025.06.006. Epub 2025 Jun 12.
Paroxysmal exercise-induced dyskinesia (PED) is a rare movement disorder characterized by choreoathetosis and dystonia triggered by sustained exercise, commonly affecting the lower extremities. PED is an autosomal dominant disorder genetically linked to mutations in the SLC2A1 gene. The transmembrane protein Glut1, encoded by the SLC2A1 gene, can transport glucose from blood to the brain. This study aimed to characterize the genetic and clinical features of SLC2A1-related PED.
We reported two Chinese PED families presenting with involuntary movements after prolonged exercise. Whole-exome sequencing was performed on two probands, and cosegregation analysis was subsequently carried out in available family members. Additionally, we summarized and analyzed the genetic and clinical features of SLC2A1-related PED by retrieving information from the literature.
Genetic testing identified two missense mutations in SLC2A1 in these families, including a known disease-causing mutation, c.997C>T (p.R333W), and a novel mutation, c.823G>C (p.A275P). Upon review of the literature, mutations in certain regions of the Glut1 protein, particularly in transmembrane segments 3, 4, 5, 7, and 8, together with the intracellular domain, were more frequently seen in PED. Among the various types of epilepsy, absence seizures were the most common in patients with PED. Furthermore, familial PED had a later onset and a higher cerebrospinal fluid/blood glucose ratio. Patients with missense mutations exhibited a later onset than those with truncated mutations.
Our study identified a new disease-causing mutation and, through an extensive literature review, provided a detailed genetic and clinical description of PED associated with SLC2A1 mutations.
