Phosphoglycerate Kinase (PGK) Deficiency

Synonyms: Phosphoglycerokinase deficiency, PGK deficiency, Haemolytic anaemia with PGK Deficiency, Erythrocyte phosphoglycerate kinase deficiency, Glycogen storage disease IX, Glycogenosis type IX.

Phosphoglycerate kinase deficiency is a hereditary metabolic muscle disease. There are two distinct syndromes. There is a pure muscle syndrome characterized by recurrent cramps and muscle breakdown in response to intense exercise, and a "muscle plus" syndrome which may feature mental retardation and/or haemolytic anaemia. Phosphoglycerate kinase is a complex enzyme. Several subtypes of phosphoglycerate kinase deficiency have been identified,¹ based on the tissues in which the enzyme deficiency occurs, and the type of inheritance.

It is rare. It is an X-linked recessive in nearly 75%. Females are carriers and have a 50% chance of transmitting the gene to an affected son or a carrier daughter. Males would have carrier daughters and unaffected sons. It is inherited as an autosomal recessive in about 25%.²

• Presentation is variable but between infancy and adolescence.
• Clinical findings include muscle pain and weakness, with muscle damage and rust-coloured urine after vigorous exercise due to myoglobinuria.
• Other symptoms are rare and highly variable but may include nausea after exercise, variable degrees of mental retardation, seizures and haemolytic anaemia. Some patients may have a purely myopathic syndrome with progressive proximal muscle weakness and episodes of myoglobinuria, exercise intolerance, and easy fatigue.
• There can be emotional lability, aphasia with impaired ability to comprehend speech or writing, muscle weakness after exercise or hemiplegia.
• Female carriers may have haemolytic anaemia.

Signs

• The most common features are enlarged liver, growth retardation, mild delay in motor development and elevated blood lipids.
• There may be splenomegaly.
• All of the symptoms usually improve as the child ages, and most adults are of normal height.

It may resemble other types of glycogen storage diseases. There are a number of enzyme defects that can cause myoglobinuria³ as well as other causes:

• Hypokalaemia, hypophosphataemia, myopathies, Acetyl-CoA dehydrogenase deficiency, and lactate dehydrogenase deficiency
• Polymyositis and dermatomyositis
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Crush syndrome
• Muscle ischaemia secondary to arterial occlusion or insufficiency
• Septicaemia
• Drug abuse

Diagnostic testing is available for the absence of the enzyme phosphoglycerate kinase. There is recurrent myoglobinuria, especially after exercise and high or normal serum CK level. Anaerobic exercise produces no rise in lactate.

Non-Drug

Strenuous exercise should be avoided.

Drugs

None are of proven value.

Surgery

Splenectomy can reduce the haemolytic anaemia and the need for transfusion.⁴

Myoglobinuria from prolonged exercise can produce renal damage.

Severity varies, but myopathic syndrome is usually slowly progressive. In one study of a large family many sufferers died before reaching adulthood.⁵

Identification of the gene⁶ may permit prenatal diagnosis with a view to termination of pregnancy.