Introduction

If you’re concerned about Pyruvate Kinase Deficiency (PKD) in your unborn child, genetic testing and medical counselling can provide you and your partner with guidance and clarity. 

PKD is an autosomal recessive disorder, meaning your child must have inherited a defective copy of a gene from both the mother and father, therefore developing this condition. This is known as an autosomal recessive disorder, and it affects 1 in 4 individuals. If you are worried this disease could affect your future children, this article will provide you with the basics of what PKD is, how it occurs, prenatal diagnosis, and how you can approach the matter. 

What is PKD and how can it be tested prenatally

PKD is a rare inherited condition affecting red blood cells, leading to chronic haemolytic anaemia. This disorder occurs from a mutation in the Pyruvate Kinase Liver Red blood cell gene, the PK-LR gene, which is protein-coding, meaning the gene causes function. However, in the case of a mutated PKLR gene, individuals with this are deficient in the enzyme pyruvate kinase. Without this enzyme, glucose, a chemical needed to provide energy, is unable to be broken down and produced. This lack of an enzyme leads to the cells in the body having less energy, and in the case of red blood cells, lacking the energy to move nutrients and oxygen around the body, but also causing haemolysis.¹

Benefits of prenatal testing

Prenatal genetic testing offers several benefits for families at risk of inherited conditions like PKD. One of the main advantages is the ability to have an early diagnosis of potential genetic disorders during the early stages of pregnancy. This allows families to prepare and plan ahead of time medically and emotionally. 

Types of tests

Prenatal diagnosis for PKD involves genetic testing to identify any mutations in the PKLR gene, which is responsible for this disorder. Two invasive methods for testing are Chorionic Villus Sampling (CVS) and amniocentesis, both of which have a low risk of causing a miscarriage. A non-invasive method of testing, known as noninvasive prenatal testing (NIPT), can also be used.²

CVS: This procedure can be conducted between 10 to 13 weeks of pregnancy, where a small tissue sample from the placenta is collected and tested for genetic abnormalities and has an accuracy rate of 99.6% in detecting mutations. 

Amniocentesis: This procedure uses the amniotic fluid, drawn from a needle using ultrasound for guidance, and is performed around 15 to 20 weeks during pregnancy. It also is a highly reliable method. 

NIPT: it uses a blood test from the mother as cell-free DNA sheds from the placenta into the mother's bloodstream and is then able to be analysed to screen for any abnormalities in the foetus. NIPT is a screening test rather than diagnostic, so it may produce false positives.

What is genetic counselling

Genetic counselling is not the same as psychological counselling. These counselling sessions are carried out by clinical geneticists or genetic counsellors. These specialists will talk you through understanding the likelihood of passing down PKD to your children, how genetic testing is performed and whether or not you would like to go through with it by listing the pros and cons and how the results are interpreted. After completion of these sessions, it is then your choice if you’d like to carry out the procedures. In the UK, genetic testing is available through the NHS. As soon-to-be parents, understanding the implications of PKD and available testing methods is important to understand.³

Counselling topics 

Your genetic counsellor will go through a series of topics to empower your knowledge of how autosomal recessive disorders are passed down. They will also advise you on whether or not to terminate the pregnancy or not. If you are looking to conceive, reproductive options like In Vitro Fertilisation will be discussed, as with preimplantation genetic testing can be done, and selected embryos without the mutated genes can be selected for implantation for future pregnancies. Carrier testing on siblings and relatives would be advised. Counsellors can also provide you with support resources by connecting you with PKD patient advocacy groups and different support groups. 

Ethical and emotional consideration

Any type of diagnosis affecting the health of your child or future children can be overwhelming, with worries they may not be able to live a normal life. Parents face the difficult question of whether or not to continue the pregnancy. A solution to this is ethical counselling to help families navigate the challenge and prepare them for the best. 

Resources and support for families 

Here are UK-based support services for families and children with rare diseases and genetic conditions. 

• Rare Disease UK 
• Metabolic Support UK 
• Antenatal Results and Choices 
• Know PK Deficiency

Summary

Pyruvate kinase deficiency is a rare genetic disorder where there is a mutation in the PKLR gene. It can be identified in the early stages of pregnancy through prenatal genetic testing. Genetic counselling is advised for couples who may be at risk of passing on mutated genes to their children. During counselling the counsellor will advise you on different prenatal tests that are available to you and talk you through how they take place, the risks that come with them and the interpretation of the results from the tests. Techniques for genetic testing currently available are chorionic villus sampling, amniocentesis, and noninvasive prenatal testing, all of which provide insight into whether your unborn child carries a mutated PKLR gene.