Rare Pulmonology News

Disease Profile

Pyruvate kinase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

D55.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pyruvate kinase deficiency of red cells; Pyruvate kinase deficiency of erythrocytes; PK deficiency

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders

Summary

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]

Symptoms

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]

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.

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

Cause

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]

Diagnosis

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.

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.

    Treatment

    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.
    https://emedicine.medscape.com/article/125096-treatment#showall

    Organizations

    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

        Learn more

        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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Pyruvate kinase deficiency. This website is maintained by the National Library of Medicine.
        • 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

              References

              1. Haldeman-Englert C. Pyruvate kinase deficiency. MedlinePlus Encyclopedia. 2/3/2014; https://www.nlm.nih.gov/medlineplus/ency/article/001197.htm.
              2. Pyruvate Kinase Deficiency. National Organization for Rare Disorders (NORD). 2005; https://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; https://www.ncbi.nlm.nih.gov/pubmed/17360088. Accessed 7/18/2011.
              5. Hassan M Yaish, MD. Pyruvate Kinase Deficiency. Medscape. April 28, 2014; https://emedicine.medscape.com/article/2196589-overview.
              6. Durand PM, Coetzer TL. Pyruvate kinase deficiency protects against. Haematologica. June 2008; https://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. .

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