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Genetic and Rare Diseases Information Center (GARD)

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Pyruvate kinase deficiency


Other Names for this Disease
  • PK deficiency
  • Pyruvate kinase deficiency of erythrocytes
  • Pyruvate kinase deficiency of red cells
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Your Question

My granddaughter has been diagnosed with pyruvate kinase deficiency. I have many questions about this condition, including how many people may be affected and if it is more common in any particular population. Any information you could provide would be helpful.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is pyruvate kinase deficiency?

Pyruvate kinase deficiency is a hereditary 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] Signs and symptoms include jaundice, enlargement of the spleen, and mild or severe hemolysis (red cell breakdown), leading to anemia.[2] Problems may first appear in the newborn as 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] Pyruvate kinase deficiency is caused by a mutation in the PKLR gene and is inherited in an autosomal recessive fashion.[1][3] 
Last updated: 7/18/2011

How many people have pyruvate kinase deficiency?

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.[4] 
Last updated: 1/14/2009

Is pyruvate kinase deficiency more common in any particular population?

Although pyruvate kinase deficiency occurs worldwide, most cases have been reported in northern Europe and Japan, as well as in the United States.[5] Certain populations, such as the Amish, are somewhat more likely to develop this condition.[1] The particular mutation responsible for the deficiency differs between populations.[5]
Last updated: 7/18/2011

What are the signs and symptoms of pyruvate kinase deficiency?

The signs and symptoms of pyruvate kinase deficiency include the breakdown of red blood cells resulting in hemolytic anemia, a yellowing of the whites of th eyes (icterus), fatigue, lethargy, recurrent gallstones, jaundice, and pale skin (pallor).[1] 
Last updated: 7/18/2011

What causes pyruvate kinase deficiency?

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, 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

How is pyruvate kinase deficiency inherited?

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.[3]  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

How might pyruvate kinase deficiency be treated?

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

What is the prognosis for individuals with pyruvate kinase deficiency?

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

References