Glycogen storage disease due to phosphoglycerate kinase 1 deficiency

Glycogen storage disease due to phosphoglycerate kinase 1 (PGK1) deficiency is a rare inherited metabolic disorder caused by mutations in the PGK1 gene, which encodes the enzyme phosphoglycerate kinase 1. This enzyme plays a critical role in glycolysis, the metabolic pathway that breaks down glucose for energy. Because PGK1 is expressed in all cells, its deficiency can affect multiple organ systems, though the clinical presentation is notably variable. The condition is also known as PGK1 deficiency or glycogen storage disease type IX (in some older classifications). The disease can manifest with three major clinical features, occurring alone or in combination: chronic hemolytic anemia, myopathy (skeletal muscle dysfunction with exercise intolerance, cramps, and sometimes rhabdomyolysis), and central nervous system involvement including intellectual disability, seizures, and other neurological abnormalities. Hemolytic anemia results from the inability of red blood cells to generate adequate energy through glycolysis, leading to premature red blood cell destruction. Myopathy may present with exercise-induced muscle pain, weakness, and episodes of myoglobinuria. Some patients exhibit all three features, while others may present with only one or two components, making diagnosis challenging. There is currently no specific curative treatment for PGK1 deficiency. Management is supportive and symptom-based. For hemolytic anemia, blood transfusions may be required, and folic acid supplementation is often recommended. Patients with myopathy are advised to avoid strenuous exercise and manage episodes of rhabdomyolysis with hydration and monitoring of kidney function. Neurological symptoms are managed with standard approaches including antiepileptic medications when seizures are present. Genetic counseling is recommended for affected families.

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