COASY variant as a new genetic cause of riboflavin-responsive lipid storage myopathy
Yilei Zheng, Tongling Liufu, Bing Wen, Chao Zhou, Lingchun Liu, Yusen Qiu, Wen‐Quan Zou, Wei Zhang, Yu Li, Jianfeng Pei, Yi‐Heng Zeng, Wan‐Jin Chen, Chunhua Zhang, Yun Yuan, Guochun Wang, Chuanzhu Yan, Xin Lü, Jianwen Deng, Zhaoxia Wang, Daojun Hong
Abstract
Human coenzyme A synthase ( COASY ) encodes a bifunctional enzyme containing 4’PP adenyltransferase (PPAT) and dephospho-CoA kinase (DPCK) domains that catalyzes the last two steps of de novo CoA biosynthesis (Supplementary Fig. S1 ) 1 . Biallelic COASY variants have been associated with severe neurodegenerative diseases 2 , 3 . However, no muscular disorders associated with COASY have been reported until now. Here, we found that biallelic COASY variants can be a novel genetic cause of riboflavin-responsive lipid storage myopathy (RR-LSM). RR-LSM is a subtype of lipid metabolic disorders with onset age ranging from infancy to adulthood. It is characterized by muscle weakness or exercise intolerance sometimes triggered by precipitating factors, occasional extramuscular multi-system symptoms, excessive accumulation of lipid droplets (LDs) in myofibers, and dramatic responsiveness to riboflavin 4 . Although genetic causes of the majority of the disorders have been identified, those for late-onset RR-LSM remain unresolved.