How is Pyruvate Kinase Deficiency inherited?

We’ve had the chance to interview Dr. Richard Van Wijk about the genetic aspect of Pyruvate Kinase Deficiency. Dr. Van Wijk is staff member of the Department of Clinical Chemistry and Haematology at the University Medical Center in Utrecht, The Netherlands. He is closely involved in the research and laboratory diagnosis of benign disorders of the red blood cell, in particular haemolytic anaemia.

How is Pyruvate Kinase Deficiency inherited?

Dr. Van Wijk: The inheritance pattern of Pyruvate Kinase Deficiency is autosomal recessive. Generally everybody carries 2 copies of a gene. So, everybody has 2 copies of the PK gene. A person who has one normal Pyruvate Kinase gene and one mutant  Pyruvate Kinase gene is a carrier of the disease. Such persons generally do not show any symptoms.

The chance for each carrier to transmit the gene for the disease is 50%. When both parents are carriers, there is a 25% chance that both genes for disease are transmitted to the child. In that case the child will have two genes for disease and will have Pyruvate Kinase Deficiency. There is also a 25% chance that the child will not carry any abnormal gene. Finally, there is a 50% chance that the child will inherit only one gene for disease (either the one from the mother or the one from the father). In this case, the child will be a carrier of the Pyruvate  Kinase Deficiency, the risks are the same for each pregnancy.

How many people have Pyruvate Kinase Deficiency ? In which part of the world is it most common?

Dr. Van Wijk: There are more than 600 Pyruvate Kinase Deficiency families reported in the literature but there are many more patients. The true frequency of Pyruvate Kinase Deficiency however is unknown because national registries are rare and international registries do not exist. Pyruvate Kinase Deficiency occurs worldwide but seems to occur more frequently in the Caucasian population. A sophisticated study from the year 2000 estimated the number of Pyruvate Kinase Deficiency  patients at 51 per 1,000,000 in the general white population. On the other hand, both the Dutch and Italian Pyruvate Kinase Deficiency registries suggest a frequency that is about 10 times lower. This illustrates that it is difficult to determine the true number of Pyruvate Kinase Deficiency patients. Also of importance in this regard is the fact that probably not all patients with  Pyruvate Kinase Deficiency are diagnosed. This can be, for example, because they are only mildly affected and further diagnostic testing is not performed. Also, the specific diagnostic tests to diagnose PKD are not available to every patient around the world.

How many different Pyruvate Kinase Deficiency mutations are there? What are the differences between the genes?

Dr. Van Wijk: The scientific literature reports more than 200 different mutations causing Pyruvate Kinase Deficiency. All these mutations affect one single gene (the PKLR gene). This gene codes for a protein called pyruvate kinase. This protein is important for red blood cells to stay healthy. In Pyruvate Kinase Deficiency, the protein does not function properly and the red blood cell lives considerably shorter than normal. All the known mutations affect the same protein, but at a different place or in a different way. The end result however is the same for all mutations: less functional protein.

(A public database of mutations is available at

Some Pyruvate Kinase Deficiency patients are very depended on transfusions others hardly have any, is there a difference in their genes?

Dr. Van Wijk: This is an important question but rather difficult to answer. It is definitely true that some mutations have a more severe effect than others. This can be concluded from Pyruvate Kinase Deficiency   patients who have inherited the same mutation from the mother and the father (they are called homozygous). But because there are so many different mutations causing Pyruvate Kinase Deficiency most patients have an unique combination of two different mutations. This makes it very difficult to study the effect of specific mutations on the clinical outcome, including the need for blood transfusions.

Is it true that Pyruvate Kinase Deficiency patients are immune for malaria? And if so, why?

Dr. Van Wijk: I would not state that Pyruvate Kinase Deficiency patients are immune to malaria. There is evidence in the scientific literature though that Pyruvate Kinase Deficiency may protect against infection with the malaria parasite. The malaria parasite doesn’t seem to grow and survive as well in PKD red blood cells as it does in normal red blood cells. This may decrease the risk of infection with the malaria parasite.

Does Pyruvate Kinase Deficiency affect males and females with different symptoms?

Dr. Van Wijk: No, males and females are affected in the same way. The only gender difference would be the aggrevation of anemia during pregnancy.

Will biological children of Pyruvate Kinase Deficiency  patients get the disease?

Dr. Van Wijk:  Pyruvate Kinase Deficiency  patients will always transmit one of their two disease genes to their biological children. Assuming that their spouses have two normal genes, their children will always be carriers. However, biological children of Pyruvate Kinase Deficiency patients can also get PKD when their spouse is a asymptomatic carrier or a PKD patient. For further information on this a genetic counselling service should be consulted.

Is it possible to test the genes of your partner?

Dr. Van Wijk: Yes, partners can be screened for mutations in the gene that causes  Pyruvate Kinase Deficiency . This is the same test as used for patients with PKD.

Dr. Richard Van Wijk
Assistant professor
University Medical Center Utrecht
Heidelberglaan 100 3583CX Utrecht • Netherlands

Disclaimer: This article is written by patients and is meant for basic informational purposes only. It is not intended to serve as medical advice, substitute for a doctor's appointment or to be used for diagnosing or treating a disease. Users of this website are advised to consult with their physician before making any decisions concerning their health. For details see our full disclaimer.

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