PFKM gene

At least 20 mutations in the PFKM gene have been found to cause glycogen storage disease type VII (GSDVII). This condition is characterized by an inability to break down glycogen in muscle cells, resulting in muscle cramps and weakness that can vary in severity among affected individuals. PFKM gene mutations that cause GSDVII result in the production of PFKM subunits that have little or no function. One PFKM gene mutation accounts for most cases of GSDVII in people with Ashkenazi Jewish ancestry. This mutation (written as IVS5+1G>A) results in a small deletion of genetic material within the gene, which alters the way the gene's instructions are pieced together and causes a nonfunctional subunit to be produced.

Without functional PFKM subunits, no functional phosphofructokinase is formed in skeletal muscles and glycogen cannot be completely broken down. Partially broken down glycogen builds up in muscle cells. Muscles that do not have access to glycogen as an energy source become weakened and cramped following moderate strain, such as exercise, and in some cases, begin to break down. In other tissues, other subunits that make up the phosphofructokinase enzyme likely compensate for the lack of PFKM subunits, and the enzyme is able to retain some function. This compensation may help explain why other tissues are not affected by PFKM gene mutations. It is unclear why some individuals with GSDVII are more severely affected than others.