Pyruvate Kinase Deficiency

What is pyruvate kinase (PK) deficiency?

Pyruvate kinase (PK) deficiency is a rare genetic disorder in which red blood cells break down too quickly, leading to chronic anemia. A person must have two variants in the PKLR gene, or two copies of a variant, in order to have this condition. People with just one variant in the PKLR gene are called carriers. They’re not expected to have PK deficiency themselves, but they could pass their variant on to their future children.

The genetics behind PK deficiency

PK deficiency is caused by variants (differences) in the PKLR gene. The PKLR gene contains instructions for making an enzyme called pyruvate kinase, or PK. This enzyme is found primarily in red blood cells and liver cells, where it plays an important role in breaking down glucose to produce energy. Certain variants in the PKLR gene disrupt the function of the PK enzyme, leading to the premature destruction of red blood cells (called hemolytic anemia).

What are the symptoms of PK deficiency?

Symptoms of PK deficiency include chronic anemia; extreme fatigue and difficulty exercising; jaundice (yellowing of the skin and eyes); cognitive difficulties such as difficulty concentrating; enlarged spleen; iron overload; and gallstones. Symptoms can develop anytime from before birth to adulthood and can vary from mild to severe. Symptoms may also worsen with age.

Did you know?

PK deficiency is found in people of many ethnicities. It is estimated that about 1 in 20,000 people of European descent has the condition. PK deficiency is more common in the Amish and Roma communities.

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The 23andMe Pyruvate Kinase Deficiency Carrier Status report* can tell you whether you may be a carrier for PK deficiency. Being a carrier means you have a genetic variant that you could pass down to your future children. 23andMe tests for one variant in the PKLR gene linked to PK deficiency. 23andMe does not test for all possible genetic variants linked to PK deficiency, and the report does not include the majority of PKLR variants that cause PK deficiency in any ethnicity. Individuals who have zero variants detected still have a chance of being a carrier for PK deficiency.

The Pyruvate Kinase Deficiency Carrier Status report is included in the 23andMe Health + Ancestry Service.

*The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults for the purpose of reporting carrier status and reporting and interpreting genetic health risks. The relevance of each report may vary based on ethnicity. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future or anything about the health of your fetus, or your newborn child’s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. The Pyruvate Kinase Deficiency carrier status report is indicated for the detection of the R486W variant in the PKLR gene. The report can tell you if you have two copies of the R486W variant, and if you are at risk of developing symptoms of pyruvate kinase deficiency, but does not describe your overall risk of developing symptoms.

References

Beutler E et al. (2000). “Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population.” Blood. 95(11):3585-8.

Bianchi P et al. (2020). “Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency.” Am J Hematol. 95(5):472-482.

Genetic and Rare Diseases Information Center. “Pyruvate kinase deficiency.” Retrieved Apr 29, 2021, from https://rarediseases.info.nih.gov/diseases/7514/pyruvate-kinase-deficiency. 

MedlinePlus. “Pyruvate kinase deficiency.” Retrieved Apr 29, 2021, from https://medlineplus.gov/genetics/condition/pyruvate-kinase-deficiency/. 

National Organization for Rare Disorders. “Pyruvate Kinase Deficiency.” Retrieved Apr 29, 2021, from https://rarediseases.org/rare-diseases/pyruvate-kinase-deficiency/.