Pyruvate Kinase Deficiency

Pyruvate Kinase Deficiency

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Pyruvate Kinase Deficiency is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Nonspherocytic Hemolytic Anemia, Congenital with low PK Kinetics

Disorder Subdivisions

  • None

General Discussion

Red cell pyruvate kinase deficiency is a hereditary blood disorder characterized by a deficiency of the enzyme pyruvate kinase. Physical findings associated with the disorder may include reduced levels of oxygen-carrying hemoglobulin in the blood due to premature destruction of red blood cells (hemolytic anemia); abnormally increased levels of bilirubin in the blood (hyperbilirubinemia); abnormal enlargement of the spleen (splenomegaly); and/or other abnormalities. Pyruvate kinase deficiency is inherited as an autosomal recessive genetic trait. It is one of a group of diseases known as hereditary nonspherocytic hemolytic anemias. (Nonspherocytic refers to the fact that the red blood cells do not assume a spherical shape, as they do with some blood disorders.

Symptoms

Pyruvate kinase deficiency is characterized by hemolytic anemia. An excess of young red blood cells (reticulocytes) usually occurs. The anemia is chronic and may vary from mild to severe. Enlargement of the spleen (splenomegaly) may occur, and gallstones may sometimes develop. After infections, the anemia tends to become more severe. In rare cases, leg ulcers may develop.

Causes

Pyruvate kinase deficiency is inherited in an autosomal-recessive manner. It is caused by mutations of the PKLR gene, the gene that encodes the liver and red cell type of pyruvate kinase. The gene is located on chromosome 1 (1q21).



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 1q21 refers to band 21 on the long arm of chromosome 1. 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.

Affected Populations

The incidence of pyruvate kinase deficiency is less than 1% of the population. Males and females are affected in equal numbers. Most affected persons identified thus far have been of European origin.

Standard Therapies

Diagnosis

A physical examination that reveals an enlarged spleen in the presence of jaundice is usually sufficient to trigger a call for more definitive tests. A complete blood count, differential blood counts, and reticulocyte counts may be undertaken. Tests for the presence of bile salts (bilirubin) are used to determine whether the gall bladder is involved. DNA analysis may be ordered to confirm the diagnosis.



Treatment

Mild cases require no treatment. More severe disease is usually treated with blood transfusions. Surgical removal of the spleen (splenectomy) may also be needed. With small children, this is delayed as long as possible to allow the immune system to mature. Other treatment is symptomatic and supportive.

Investigational Therapies

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

References

TEXTBOOKS

Beutler E. Pyruvate Kinase Deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:496-97.



Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:4638-44.



Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:859.



JOURNAL ARTICLES

Aizawa S, Kohdera U, Hiramoto M, et al. Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency. Am J Hematol. 2003;74:68-72.



Van Rijk R, van Solinge WW, Nerlov C, et al. Disruption of a novel regulatory element in the erythroid-specific promoter of the human PKLR gene causes severe pyruvate kinase deficiency. Bllod. 2003;101:1596-602.



Watanabe Y, Miyauchi K, Horiuchi A, et al. Concomitant laparoscopic splenectomy and cholecystectomy as an effective and minimally invasive treatment of pyruvate kinase deficiency with gallstones. Surg Endosc. 2002;16:1495.



Valentini G, Chiarelli LR, Fortin R, et al. Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia. J Biol Chem. 2002;277:23807-14.



Zanella A, Bianchi P, Fermo E, et al. Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients. Br J Haematol. 2001;113:43-48.



Tanphaichitr VS, Suvatte V, Issaragrisil S, et al. Successful bone marrow transplantation in a child with red blood cell pyruvate kinase deficiency. Bone Marrow Transplant. 2000;26:689-90.



Zanella A, Bianchi P. Red cell pyruvate kinase deficiency: from genetics to clinical manifestations. Baillieres Best Pract Res Clin Haematol. 2000;13:57-81.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Pyruvate Kinase Deficiency of Erythrocyte. Entry Number; 266200: Last Edit Date; 1/21/2005.



McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Pyruvate Kinase 3; PK3. Entry Number; 179050: Last Edit Date; 7/17/2003.



Stewart DR. Pyruvate kinase deficiency. Medical Encyclopedia. MedlinePlus. Update Date: 7/26/2004. 2pp.

www.nlm.nih.gov/medlineplus/ency/001197



Yaish HM. Pyruvate Kinase Deficiency. emedicine. Last Updated: December 9, 2004. 11pp.

www.emedicine.com/ped/topic1971/htm



Frye RE, DeLaughery TG. Pyruvate Kinase Deficiency. emedicine. Last Updated. February 4, 2005. 12pp.

www.emedicine.com/med/topic1980.htm



Max-Audit I. Pyruvate kinase deficiency. Orphanet. December 2001. 1p.

www.orpha.net/consor/cgi-bin/printer.php

Resources

Lactic Acidosis Support Trust

1A Whitley Close

Middlewich

Cheshire, CW10 0NQ

United Kingdom

Tel: 0160683719

Fax: 01606837198



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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