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Synonyms: Phosphoglycerokinase deficiency, PGK deficiency, PGK1 deficiency, Haemolytic anaemia with PGK Deficiency,

Phosphoglycerate kinase deficiency is a hereditary metabolic disease. Phosphoglycerate kinase (PGK1) is a ubiquitous glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate generating one molecule of ATP. Its gene lies on the X-chromosome (locus Xq13) and there are related pseudogenes on the X-chromosome and chromosome 19.[1]

It is a complex enzyme: several subtypes of deficiency have been identified,[2] based on the tissues in which the enzyme deficiency occurs and the type of inheritance. Clinically, there are two distinct syndromes:

  • A pure muscle syndrome characterized by recurrent cramps and muscle breakdown in response to intense exercise.[3]
  • A "muscle plus" syndrome which may feature mental retardation and/or haemolytic anaemia.

Different mutations of the erythrocyte enzyme PGK1 gene have been identified but the reason for the multifarious clinical manifestations of mutations of the same gene remains unknown.[4]

  • It is extremely rare.
  • The gene encoding the erythrocyte enzyme PGK1 is X-linked and PGK is transmitted as an X-linked recessive disorder in nearly 75%. Females are carriers and have a 50% chance of transmitting the gene to an affected son or a carrier daughter. Affected males produce carrier daughters and unaffected sons.
  • It is inherited as an autosomal recessive in about 25%.[5]
  • Presentation is variable but occurs between infancy and adolescence.
  • Clinical findings include:
    • Muscle pain and weakness
    • Rust-coloured urine after vigorous exercise due to myoglobinuria
  • Other features are rare and highly variable but may include:
  • 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 and hemiplegia.
  • Female carriers may have haemolytic anaemia.

There are a number of enzyme defects that can cause myoglobinuria[6] as well as other causes to remember:

  • Diagnostic testing is available for the absence of the enzyme phosphoglycerate kinase.
  • There is recurrent myoglobinuria, especially after exercise.
  • Serum CK levels are high or normal.
  • Anaerobic exercise produces no rise in lactate.
  • Gene mutation identification within family groups.


Strenuous exercise should be avoided.


None are of proven value.


Splenectomy can reduce the haemolytic anaemia and the need for transfusion.[7]

Myoglobinuria from prolonged exercise can produce renal damage.

Severity varies but the myopathic syndrome is usually slowly progressive. In one study of a large family, many sufferers died before reaching adulthood.[8]

Identification of the gene[9] may permit prenatal diagnosis with a view to termination of pregnancy.

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Further reading and references

  1. Phosphoglycerate Kinase-1 Deficiency, Online Mendelian Inheritance in Man (OMIM)

  2. Tsujino S, Shanske S, DiMauro S; Molecular genetic heterogeneity of phosphoglycerate kinase (PGK) deficiency. Muscle Nerve. 19953:S45-9.

  3. Spiegel R, Gomez EA, Akman HO, et al; Myopathic form of phosphoglycerate kinase (PGK) deficiency: A new case and pathogenic considerations. Neuromuscul Disord. 2009 Jan 19.

  4. Beutler E; PGK deficiency. Br J Haematol. 2007 Jan136(1):3-11.

  5. Phosphoglycerate Kinase (PGK) 1 Deficiency, Online Mendelian Inheritance in Man (OMIM)

  6. Tonin P, Lewis P, Servidei S, et al; Metabolic causes of myoglobinuria. Ann Neurol. 1990 Feb27(2):181-5.

  7. Fujii H, Miwa S; Other erythrocyte enzyme deficiencies associated with non-haematological symptoms: phosphoglycerate kinase and phosphofructokinase deficiency. Baillieres Best Pract Res Clin Haematol. 2000 Mar13(1):141-8.

  8. Turner G, Fletcher J, Elber J, et al; Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred. Br J Haematol. 1995 Sep91(1):60-5.

  9. Flanagan JM, Rhodes M, Wilson M, et al; The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA. Br J Haematol. 2006 Jul134(2):233-7. Epub 2006 Jun 1.