Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptoms

Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts. This is the first family with more than one affected case of PGK deficiency and exercise-induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle's disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui's disease: glycogenosis Type VII). PGK deficiency is inherited as an X-linked trait and may show other features such as mental retardation and/or haemolytic anaemia.