You are here: Home / Rare Disease Information / Rare Disease Database

Search Rare Diseases

Enter a disease name or synonym to search NORD's database of reports.

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

Phosphoglycerate Kinase Deficiency

NORD is very grateful to Jan O. Aasly, MD, PhD, Consultant Neurologist/Professor of Neurology, Department of Neurology, St. Olav's Hospital, for assistance in the preparation of this report.

Synonyms of Phosphoglycerate Kinase Deficiency

  • anemia, hemolytic with PGK deficiency
  • erythrocyte phosphoglycerate kinase deficiency
  • PGK
  • phosphoglycerokinase

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Phosphoglycerate kinase deficiency is an extremely rare inherited metabolic disorder characterized by deficiency of the enzyme phosphoglycerate kinase. This enzyme is essential for the breakdown of glycogen, resulting in the release of energy. Symptoms and findings associated with the disorder may include low levels of circulating red blood cells (hemolytic anemia); varying degrees of intellectual disability; rapidly changing emotions (emotional lability); an impaired ability to communicate through and/or to comprehend speech or writing (aphasia); exercise-induced pain, stiffness, or cramps; enlargement of the spleen (splenomegaly); and/or paralysis of one side of the body (hemiplegia). In most cases, phosphoglycerate kinase deficiency is inherited as an X-linked genetic trait. In such cases, the disorder is fully expressed in males only; however, some females who carry one copy of the disease gene (heterozygotes) may have hemolytic anemia.

Symptoms

The three main features of phosphoglycerate kinase deficiency are hemolytic anemia, intellectual disability, and muscle problems (myopathy). An individual with the disorder may be affected by one or more of these features, but it is unusual for one person to exhibit all three signs.

Individuals with childhood PGK deficiency have some degree of intellectual disability with delayed language acquisition. Some have epilepsy and strokes.

Most adult patients are moderately affected, and heterozygous females may show only mild hemolytic anemia with no myopathy or intellectual disability.

Myopathy with exercise-induced stiffness, cramps, and muscle pain is seen in adolescents and young adult males. The cramps are often severe and may incapacitate the individual for hours, sometimes followed by myoglobinuria.

Causes

PGK is considered to be an inborn error of metabolism that is inherited in an X-linked recessive manner. The gene responsible is located on the X chromosome (Xq13).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome Xq13" refers to band 13 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off' and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

Affected Populations

Phosphoglycerate kinase deficiency is a very rare disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygous carriers) may exhibit some symptoms associated with the disorder (i.e., hemolytic anemia). The disorder can be diagnosed at birth when enzymatic testing is done. More than 30 cases of PGK deficiency have been written up in the medical literature. It is thought that there are people with the disease who do not receive a diagnosis.

Related Disorders

Symptoms of the following disorders can be similar to those of phosphoglycerate kinase deficiency. Comparisons may be useful for a differential diagnosis:

Warm antibody hemolytic anemia is an autoimmune disorder characterized by the premature destruction of red blood cells by the body's natural defenses against invading organisms (antibodies). The severity of the anemia is determined by the amount of time the red blood cells survive. (For more information on this disorder, choose "Warm Antibody, Hemolytic Anemia" as your search term in the Rare Disease Database.)

Acquired autoimmune hemolytic anemia is an autoimmune disorder characterized by the premature destruction of red blood cells. It occurs in individuals who previously had a normal red blood cell system. The disorder commonly occurs as the result of, or in conjunction with some other medical condition. (For more information on this disorder, choose "Acquired Autoimmune Hemolytic Anemia" as your search term in the Rare Disease Database.)

Sideroblastic anemia is a blood disorder characterized by an impaired ability of the bone marrow to produce normal red blood cells. It is characterized by general weakness, fatigue and difficulty breathing. (For more information on this disorder, choose "Sideroblastic Anemia" as your search term in the Rare Disease Database.)

Aplastic anemia is characterized by bone marrow failure. The disorder may occur for unknown reasons (idiopathic) or it may be the result of a toxic reaction to radiation, certain drugs, or chemicals. The patient may first become aware of the disease by the progressive onset of weakness, fatigue, and lassitude. (For more information on this disorder, choose "Aplastic Anemia" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
The diagnosis is made on the basis of a thorough physical examination and confirmed by the results of laboratory tests.

Treatment
Treatment of phosphoglycerate kinase deficiency may consist of iron supplements and blood transfusions when needed. The avoidance of strenuous exercise when evidence that muscle breakdown has taken place is very important and special care is needed during neurologic crisis to avoid life-threatening situations. Bone marrow transplantation may be an option in cases with severe neurological deterioration.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Research on inborn errors of metabolism is ongoing. Scientists are studying the causes of these disorders and trying to design enzyme replacement therapies that will return a missing enzyme to the body.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Contact for additional information about phosphoglycerate kinase deficiency:

Jan O. Aasly, MD, Ph.D.
Consultant Neurologist/Professor of Neurology
Dept of Neurology
St. Olav’s Hospital
7006 Trondheim, Norway
Tel: +47 7257 5071
Mobile ph.: +47 951 96796
E-mail: Jan.Aasly@ntnu.no

Phosphoglycerate Kinase Deficiency Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Aasly J. Phosphoglycerate Kinase Deficiency. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins: 2003:489-90.

Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. New York, NY:; 2001:1529,1542, 4648-49.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Companies; 1998:612-13.

JOURNAL ARTICLES
Chiarelli LR, Morera SM, Bianchi P, et al. Molecular insights on pathogenic effects of mutations causing phosphoglycerate kinase deficiency. PLoS ONE. 2012;7:e32065.

Rhodes M, Ashford L, Manes B, Calder C, Domm J, Frangoul H. Bone marrow transplantation in phosphoglycerate kinase (PGK) deficiency. Br J Haematol. 2011;152:500-2.

Sotiriou E, Greene P, Krishna S, Hirano M, DiMauro S. Myopathy and parkinsonism in phosphoglycerate kinase deficiency. Muscle Nerve. 2010;41:707-10.

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;19:207-11.

Svaasand EK, Aasly J, Landsem VM, Klungland H. Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle Nerve. 2007;36:679-84.

Beutler E. PGK deficiency. Brit J Haematology. 2006;136:3-11.

Fujii H, Miwa S. Other erythrocyte enzyme deficiencies associated with non-haematological symptoms: phosphoglycerate kinase and phospho-fructokinase deficiency. Baillieres Best Pract Res Clin Hematol. 2000;13:141-48.

Aasly J, van Diggelen OP, Boer AM, et al. Phosphoglycerate Kinase Deficiency in two brothers with McArdle-like clinical symptoms. Eur J Neurol. 2000;7:111-13.

Aasly J, van Diggelen OP, Boer AM, et al. Phosphoglycerate Kinase Deficiency in two brothers with McArdle-like clinical symptoms. Eur J Neurol. 2000;7:111-13.

Tein I. Neonatal metabolic myopathies. Semin Perinatol. 1999;23:125-51.

INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Phosphoglycerate Kinase 1; PGK1. Entry No: 311800. Last Edited April 12, 2012. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed May 9, 2012.

Katirji B. Metabolic Myopathies. Emedicine. http://emedicine.medscape.com/article/1173338-overview. Last Updated: February 6, 2012. Accessed May 9, 2012.

Phosphoglycerate kinase 1 deficiency. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=713. Last Updated August 2008. Accessed May 9, 2012.

Phosphoglycerate kinase deficiency. Muscular Dystrophy Foundation. http://www.mdausa.org/disease/pgk.html. Accessed May 9, 2012.

Hesterlee S. Running on Empty. Keeping Up with Metabolic Myopathies. Muscular Dystrophy Foundation. www.mdausa.org/publications/Quest/q66metabolic.html. Accessed May 9, 2012.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2012/05/11 00:00:00 GMT+0

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.

 
Copyright ©2014 NORD - National Organization for Rare Disorders, Inc. All rights reserved.
The following trademarks/registered service marks are owned by NORD: NORD, National Organization for Rare Disorders, the NORD logo, RareConnect. .