A New 23andMe Report on Pyruvate Kinase Deficiency

23andMe recently added a new report on pyruvate kinase (PK) deficiency, a rare genetic disorder that can result in chronic anemia and other serious complications.*

This new Carrier Status report looks at one variant in the PKLR gene linked to PK deficiency. The inherited condition is autosomal recessive, meaning that a person must inherit two variants in the PKLR gene, or two copies of a variant (one from each parent), to develop the condition.

The report is meant to offer customers an opportunity to learn about their family’s potential risk for PK deficiency, while also raising awareness about this rare inherited condition.

The PKLR Gene is on Chromosome 1
More About PK Deficiency

The PKLR gene contains instructions for making the PK enzyme, which is found mostly in red blood cells and liver cells. This enzyme is crucial in breaking down glucose and producing adenosine triphosphate (ATP), the main energy source for the human body. Certain variants in the PKLR gene can disrupt the function of the PK enzyme, leading to the premature destruction of red blood cells, and ultimately a type of anemia called hemolytic anemia. [1,2]

Along with chronic anemia, the other symptoms associated with PK deficiency may include fatigue, jaundice, enlarged spleen, iron overload, and gallstones. [3,4] While there is no known cure for the condition, treatments for some of the symptoms include blood transfusions, medications to remove excess iron from the blood, and removal of the spleen and gallbladder.[3,4] Medications that increase the activity of the PK enzyme in red blood cells are also in development, as a way to treat the underlying cause of the condition. [5]

Because the symptoms of PK deficiency can vary widely and are sometimes mild, the condition may remain undiagnosed or misdiagnosed. [1,2] PK deficiency is found in people of many ethnicities, and it’s estimated that the condition affects about 1 in 20,000 people of European descent.[2]

23andMe’s New Report

23andMe’s new Pyruvate Kinase Deficiency Carrier Status report* tests for one variant linked to PK deficiency. However, there are more than 300 variants in the PKLR gene linked to the condition.[3,6] This means that customers who receive a “Variant not detected” result could still have a variant not covered by the test. Because the condition runs in families, 23andMe’s new Pyruvate Kinase Deficiency Carrier Status report gives customers an opportunity to learn more about their chances of passing a variant on to their children. For customers with a variant detected, if their partner is also a carrier for PK deficiency, each child has a 25 percent chance of having the condition. In some cases, customers may also learn that, based on their genetic result, they are at risk of developing symptoms of PK deficiency. This in turn gives them a chance to discuss the condition with their healthcare provider, and learn about potential next steps. It is important to note that 23andMe reports are not intended to diagnose any health conditions or to determine the appropriate treatment.

Because of its own commitment to raise awareness about PK deficiency, Agios Pharmaceuticals supported the development of this report. The company, a leader in the development of treatments for cancer and rare genetic diseases, has worked for many years on treatments for PK deficiency, developing a deep understanding of the impact the condition has on patients and their families. The company’s team of scientists, researchers, and patient advocates offered important insight into our development of this report.

The Pyruvate Kinase Deficiency Carrier Status report is available to 23andMe Health + Ancestry customers who are genotyped on 23andMe’s V5 chip

*The 23andMe PGS test uses qualitative genotyping to 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:
[3] Bianchi P et al. (2019). “Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency.” Am J Hematol. 94(1):149-161. https://pubmed.ncbi.nlm.nih.gov/30358897/