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Pyruvate kinase deficiency


Other Names:
Pyruvate kinase deficiency of red cells; Pyruvate kinase deficiency of erythrocytes; PK deficiency
Categories:
Pyruvate kinase deficiency is a genetic blood disorder characterized by low levels of an enzyme called pyruvate kinase, which is used by red blood cells. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia).[1] The signs and symptoms of the disease may vary greatly from person to person. However, they usually include jaundice, enlargement of the spleen, and mild or severe hemolysis (red cell breakdown), leading to anemia.[2] In some cases, the problems may first appear while in utero, causing a condition in which abnormal amounts of fluid build up in two or more body areas of the fetus (hydrops fetalis). Newborns may present with prolonged jaundice and anemia. Older children may be pale (due to anemia) and have intermittent episodes of jaundice. Mild cases may escape detection until adulthood.[1] Although the anemia tends to stabilize in adulthood, episodes of anemia may occur with acute infections, stress, and pregnancy.[3] Pyruvate kinase deficiency is caused by a mutation in the PKLR gene and is inherited in an autosomal recessive fashion.[1][4] Treatment remains supportive rather than curative.[3]



 
Last updated: 1/13/2016
The signs and symptoms of pyruvate kinase deficiency may vary greatly from person to person, but usually include the breakdown of red blood cells resulting in hemolytic anemia, a yellowing of the whites of the eyes (icterus), fatigue, lethargy, recurrent gallstones, jaundice, and pale skin (pallor).[1] 

In more severe cases, the first signs and symptoms may appear in utero in the form of hydrops fetalis, a condition in which abnormal amounts of fluid build up in two or more body areas of the fetus. Newborns may present with prolonged jaundice and anemia. Older children may be pale (due to anemia) and have intermittent episodes of jaundice. Mild cases may escape detection until adulthood.[1] Although the anemia tends to stabilize in adulthood, episodes of anemia may occur with acute infections, stress, and pregnancy.[3]
Last updated: 1/13/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Chronic hemolytic anemia 0004870
Reduced red cell pyruvate kinase level 0025109
Reticulocytosis
Increased immature red blood cells
Increased number of immature red blood cells
[ more ] 		0001923
Splenomegaly
Increased spleen size
0001744
Unconjugated hyperbilirubinemia 0008282
30%-79% of people have these symptoms
Congenital hemolytic anemia 0004804
Hydrops fetalis 0001789
Increased serum ferritin
Elevated serum ferritin
High ferritin level
Increased ferritin
Increased serum ferritin level
[ more ] 		0003281
Increased serum iron 0003452
Prolonged neonatal jaundice
Prolonged yellowing of skin in newborn
0006579
5%-29% of people have these symptoms
Anisocytosis
Unequal size of red blood cells
0011273
Elevated transferrin saturation 0012463
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Nonimmune hydrops fetalis 0001790
Poikilocytosis 0004447
Percent of people who have these symptoms is not available through HPO
Abnormality of the amniotic fluid 0001560
Autosomal recessive inheritance 0000007
Cholecystitis
Gallbladder inflammation
0001082
Cholelithiasis
Gallstones
0001081
Increased red cell osmotic fragility 0005502
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
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Last updated: 7/1/2020
In most cases, pyruvate kinase deficiency is caused by mutations in the PKLR gene.[1] More than 100 different mutation in the PKLR gene have been detected. Medical conditions, such as acute leukemia, preleukemia (myelodysplastic syndrome), and refractory sideroblastic anemia, as well as complications from chemotherapy, can cause an acquired pyruvate kinase deficiency. This type is more common and milder than the hereditary type.[5]
Last updated: 7/18/2011
Pyruvate kinase deficiency is inherited in an autosomal recessive fashion, which means that a child must inherit a gene with a disease-causing mutation from both parents to develop the disorder. The gene that causes pyruvate kinase deficiency is called the PKLR gene that is located on chromosome 1q21.[4]  Although the inheritance is clinically autosomal recessive, most affected individuals are compound heterozygous for two different mutant alleles. It is estimated that approximatly 1 in 100 people carry one copy of a disease-causing mutation in the PKLR gene.[5]  Carriers of one non-working PKLR gene usually have moderatly reduced levels of pyruvate kinase activity but do not develop clinical symptoms. It is possible that carriers of a mutant pyruvate kinase gene may have a protective advantage against malaria in areas where the disease is endemic.[6]
Last updated: 7/18/2011
Yes. GeneTests lists laboratories offering clinical genetic testing for this condition. Clinical genetic tests are ordered to help diagnose an affected person or other family members and to aid in decisions regarding medical care or reproductive issues. We recommend that you talk to your health care provider or a genetic professional to learn more about your testing options.
Last updated: 7/18/2011

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Mild cases require no treatment. People with severe anemia may need blood transfusions.  In newborns with dangerous levels of jaundice, a health care provider may recommend an exchange transfusion. Surgical removal of the spleen (splenectomy) may also be necessary to help reduce the destruction of red blood cells. However, this does not help in all cases. With small children, this is delayed as long as possible to allow the immune system to mature. Other treatment is symptomatic and supportive. Someone who had a splenectomy should receive the pneumococcal vaccine at recommended intervals. They also should receive preventive antibiotics until age 5.[2][1] 

An article from eMedicine Journal provides additional information on treatment for pyruvate kinase deficiency at the following link. You may need to register to view the article, but registration is free.
http://emedicine.medscape.com/article/125096-treatment#showall
Last updated: 7/18/2011
The prognosis varies. Some people may have few or no symtpoms, while others have severe symtpoms. People who have mild to moderate forms of pyruvate kinase deficiency tend to do very well long term.  People with more severe forms of the disease are mostly symptomatic during early childhood. Following early childhood, the condition is much better tolerated.[5] Some people may experience complications such as gallstones and stroke. Severe pneumococcal disease is a possible complication after splenectomy.[5][1]
Last updated: 7/18/2011
It is estimated that 1 in 20,000 people world-wide have pyruvate kinase deficiency.  A particularly high frequecy exists among the Pennsylvania Amish, in whom the disorder can be traced to a single immigrant couple.[7][5]
Last updated: 5/13/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Secondary PK deficiency has also been reported, occurring in the context of hematological diseases (acute/chronic leukemia, myelodysplastic syndromes and sideroblastic anemia; see these terms). In case of persistent normocytic hemolytic anemia in which hemoglobin abnormalities and antiglobulin reactions have been excluded, spherocytes are absent, and osmotic fragility is normal, the diagnosis of hereditary nonspherocytic hemolytic anemia should be considered.
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Pyruvate kinase deficiency. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Pyruvate kinase deficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Haldeman-Englert C. Pyruvate kinase deficiency. MedlinePlus Encyclopedia. 2/3/2014; http://www.nlm.nih.gov/medlineplus/ency/article/001197.htm.
  2. Pyruvate Kinase Deficiency. National Organization for Rare Disorders (NORD). 2005; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/465/viewAbstract. Accessed 7/18/2011.
  3. Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B. Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol. 2015 Sep; 90(9):825-30.
  4. Zanella A, Fermo E, Bianchi P, Chiarelli LR, Valentini G. Pyruvate kinase deficiency: the genotype-phenotype association.. Blood Rev. 2007; http://www.ncbi.nlm.nih.gov/pubmed/17360088. Accessed 7/18/2011.
  5. Hassan M Yaish, MD. Pyruvate Kinase Deficiency. Medscape. April 28, 2014; http://emedicine.medscape.com/article/2196589-overview.
  6. Durand PM, Coetzer TL. Pyruvate kinase deficiency protects against. Haematologica. June 2008; http://www.haematologica.org/cgi/reprint/haematol.12450v1. Accessed 7/18/2011.
  7. Glader Bertil E. Chapter 76. Other Hereditary Red Blood Cell Disorders. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR, eds. Emery and Rimoin's: Principles and Practices of Medical Genetics. Vol 2. 5th ed. Philadelphia, PA: Churchill Livingstone; 2007: 1675. .