Glycogen storage disease due to muscle phosphofructokinase deficiency

Glycogen storage disease due to muscle phosphofructokinase deficiency, also known as Glycogen Storage Disease Type VII (GSD VII) or Tarui disease, is a rare inherited metabolic disorder caused by deficiency of the muscle isoform of phosphofructokinase (PFK-M), a key enzyme in glycolysis. The disease was first described by Tarui and colleagues in 1965. Because PFK-M is essential for converting fructose-6-phosphate to fructose-1,6-bisphosphate during glucose metabolism, its deficiency impairs the ability of skeletal muscle to utilize glucose and glycogen as fuel, leading to glycogen accumulation in muscle tissue. The disease primarily affects the musculoskeletal system and the hematologic system. Key clinical features include exercise intolerance, muscle cramps, myalgia, and exertional myoglobinuria. Patients typically experience fatigue and weakness during vigorous physical activity. A characteristic feature is the "out-of-wind" phenomenon, where patients experience exaggerated shortness of breath and fatigue early during exercise. Because PFK-M is also partially expressed in red blood cells, patients often exhibit mild compensated hemolytic anemia with elevated reticulocyte counts and indirect bilirubin, as well as hyperuricemia. Some patients may develop a late-onset fixed proximal myopathy. An infantile form with more severe manifestations, including hypotonia, progressive myopathy, cardiomyopathy, and respiratory failure, has also been described. There is currently no specific curative treatment for GSD VII. Management is primarily supportive and involves avoidance of strenuous exercise to prevent rhabdomyolysis and myoglobinuria. Unlike some other glycogen storage diseases, a high-carbohydrate diet does not improve symptoms and may actually worsen exercise intolerance. A ketogenic or high-protein diet has been suggested by some experts to provide alternative fuel sources for muscle. Patients should be monitored for complications including gout secondary to hyperuricemia and potential renal damage from recurrent myoglobinuria.

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