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Phosphoglycerate kinase deficiency

Reviewed December 2011

What is phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major forms of the condition. The most common form is sometimes called the hemolytic form. It is characterized by a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Some people with the hemolytic form also have symptoms related to abnormal brain function, including intellectual disability, seizures, and stroke.

The other form of phosphoglycerate kinase deficiency is often called the myopathic form. It primarily affects muscles, causing progressive weakness, pain, and cramping, particularly with exercise. During exercise, muscle tissue can be broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can lead to kidney failure.

Most people with phosphoglycerate kinase deficiency have either the hemolytic form or the myopathic form. However, other combinations of signs and symptoms (such as muscle weakness with neurologic symptoms) have also been reported.

How common is phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency appears to be a rare disorder. About 30 families with affected members have been reported in the scientific literature.

What genes are related to phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency is caused by mutations in the PGK1 gene. This gene provides instructions for making an enzyme called phosphoglycerate kinase, which is involved in a critical energy-producing process in cells known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy.

Mutations in the PGK1 gene reduce the activity of phosphoglycerate kinase, which disrupts energy production and leads to cell damage or cell death. It is unclear why this abnormality preferentially affects red blood cells and brain cells in some people and muscle cells in others. Researchers speculate that different PGK1 gene mutations may have varying effects on the activity of phosphoglycerate kinase in different types of cells.

Related Gene(s)

Changes in this gene are associated with phosphoglycerate kinase deficiency.

  • PGK1

How do people inherit phosphoglycerate kinase deficiency?

This condition is inherited in an X-linked recessive pattern. The PGK1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Females with one altered PGK1 gene, however, may have some features of phosphoglycerate kinase deficiency, such as anemia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of phosphoglycerate kinase deficiency?

These resources address the diagnosis or management of phosphoglycerate kinase deficiency and may include treatment providers.

  • Children Living with Inherited Metabolic Diseases (CLIMB) (UK): Phosphoglycerate Kinase Deficiency (http://www.climb.org.uk/IMD/Papa/PhosphoglycerateKinaseDeficiency.pdf)
  • Genetic Testing Registry: Deficiency of phosphoglycerate kinase (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0684324)
  • Genetic Testing Registry: Phosphoglycerate kinase 1 deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970848)

You might also find information on the diagnosis or management of phosphoglycerate kinase deficiency in Educational resources (/condition/phosphoglycerate-kinase-deficiency/show/Educational+resources) and Patient support (/condition/phosphoglycerate-kinase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about phosphoglycerate kinase deficiency?

You may find the following resources about phosphoglycerate kinase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for phosphoglycerate kinase deficiency?

  • PGK1 deficiency
  • PGK deficiency
  • phosphoglycerate kinase 1 deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about phosphoglycerate kinase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding phosphoglycerate kinase deficiency?

anemia ; cell ; chromosome ; chronic ; deficiency ; disability ; enzyme ; gene ; glucose ; glycogen ; hemolysis ; hemolytic anemia ; inheritance ; inherited ; jaundice ; kidney ; kinase ; muscle cells ; mutation ; myoglobin ; myoglobinuria ; neurologic ; pallor ; protein ; recessive ; sex chromosomes ; simple sugar ; tissue ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (/glossary).

References

  • Aasly J, van Diggelen OP, Boer AM, Brønstad G. Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptoms. Eur J Neurol. 2000 Jan;7(1):111-3. (http://www.ncbi.nlm.nih.gov/pubmed/10809925?dopt=Abstract)
  • Beutler E. PGK deficiency. Br J Haematol. 2007 Jan;136(1):3-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17222195?dopt=Abstract)
  • Flanagan JM, Rhodes M, Wilson M, Beutler E. 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 Jul;134(2):233-7. Epub 2006 Jun 1. (http://www.ncbi.nlm.nih.gov/pubmed/16740138?dopt=Abstract)
  • Noel N, Flanagan JM, Ramirez Bajo MJ, Kalko SG, Mañú Mdel M, Garcia Fuster JL, Perez de la Ossa P, Carreras J, Beutler E, Vives Corrons JL. Two new phosphoglycerate kinase mutations associated with chronic haemolytic anaemia and neurological dysfunction in two patients from Spain. Br J Haematol. 2006 Feb;132(4):523-9. Erratum in: Br J Haematol. 2006 May;133(4):451. Flanagan, John [corrected to Flanagan, Jonathan M]; Perez de la Ossa, Pablo [added]; Carreras, Josep [added]. (http://www.ncbi.nlm.nih.gov/pubmed/16412025?dopt=Abstract)
  • Sotiriou E, Greene P, Krishna S, Hirano M, DiMauro S. Myopathy and parkinsonism in phosphoglycerate kinase deficiency. Muscle Nerve. 2010 May;41(5):707-10. doi: 10.1002/mus.21612. (http://www.ncbi.nlm.nih.gov/pubmed/20151463?dopt=Abstract)
  • Spiegel R, Gomez EA, Akman HO, Krishna S, Horovitz Y, DiMauro S. Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations. Neuromuscul Disord. 2009 Mar;19(3):207-11. doi: 10.1016/j.nmd.2008.12.004. Epub 2009 Jan 20. (http://www.ncbi.nlm.nih.gov/pubmed/19157875?dopt=Abstract)
  • Svaasand EK, Aasly J, Landsem VM, Klungland H. Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle Nerve. 2007 Nov;36(5):679-84. (http://www.ncbi.nlm.nih.gov/pubmed/17661373?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2011
Published: May 18, 2015