Phosphoglycerate Kinase Deficiency

What is Phosphoglycerate kinase deficiency (PGK deficiency)?

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. Phosphorylase kinase is a complex enzyme. Several subtypes of Phosphorylase kinase deficiency have been identified, based on which tissues the enzyme deficiency occurs, and the type of inheritance.

Are there any risk Factors?

X-linked recessive accounts for nearly 75% of cases of PGK deficiency. 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%. Some female carriers may have haemolytic anaemia.


  • 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.


  • 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.

Differential Diagnosis

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

  • Hypokalemia, hypophosphatemia, myopathies, Acetyl-CoA dehydrogenase deficiency, and lactate dehydrogenase deficiency
  • Polymyositis and dermatomyositis
  • Malignant hyperthermia
  • Neuroleptic malignant syndrome
  • Crush syndrome
  • Muscle ischemia secondary to arterial occlusion or insufficiency
  • Septicemia
  • Drug abuse


Diagnostic testing is available for the absence of the enzyme phosphoglycerate kinase. There is recurrent myoglobinuria (The presence of myoglobin in the urine), especially after exercise and therefore a urine sample may be asked for. A blood test may also be asked to look the CK levels (CK or creatine kinase, is a chemical that leaks out of the cell when muscle cells get damaged). High or normal serum CK level may be possible results for this test. Anaerobic exercise produces no rise in lactate (a compound that builds up after exercise).


At this stage there is no treatment available. Strenuous exercise should be avoided. A Splenectomy (surgery to remove the spleen) can reduce the haemolytic anaemia and the need for transfusion.


Myoglobinuria (The presence of myoglobin in the urine) from prolonged exercise can produce renal damage.


Severity varies, but myopathic syndrome is usually slowly progressive.