Pyruvate Kinase Deficiency

What else is it called?

  • PK deficiency
  • PKD

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What causes it?

Pyruvate kinase deficiency (PKD) is a genetic 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 types of cells (haemolytic anaemia). 

Pyruvate kinase deficiency is caused by faults in the PKLR gene. The PKLR gene is active in your liver and in red blood cells, where it provides instructions for making an enzyme called pyruvate kinase.  

The pyruvate kinase enzyme is involved in an energy-producing process known as glycolysis. During this process, the simple sugar glucose is broken down to produce adenosine triphosphate (ATP), the cell’s main energy source. 

If you have a fault in the PKLR gene, it means your body cannot produce enough of the pyruvate kinase enzyme. This means you do not have enough ATP in your red blood cells. When your body recognises that there is a problem with these cells, it destroys them. 

The abnormal red blood cells are maintained in the spleen and destroyed, causing red blood cells to be taken out of circulation before they should be. This causes a shortage of red blood cells in the blood, meaning that less oxygen is being transported around the body, so less oxygen can be given to tissues and cells.  

How common is it?

Pyruvate kinase deficiency is found in all ethnic groups. Its true prevalence is unknown but has been estimated at 1 in 20,000 people of European descent. It is more common in the Old Order Amish population of Pennsylvania. 

Males and females are affected in equal numbers. 

What are the signs and symptoms?

The signs and symptoms of pyruvate kinase deficiency may vary greatly from person to person, with mild compensated haemolysis at one end of the spectrum and severe transfusion-dependent anaemia from birth at the other (in some cases hydrops fetalis may occur). Symptoms usually include the breakdown of red blood cells resulting in haemolytic anaemia, shortness of breath, a yellowing of the whites of the eyes (icterus), fatigue, lethargy, recurrent gallstones, iron overload (also in non-transfused patients), jaundice, and pale skin (pallor). In some cases, Hydrops fetalis may occur. 

 80%-99% of people have these symptoms 

  • Chronic haemolytic anaemia of variable severity  
  • Reduced red cell pyruvate kinase activity 
  • An increase in immature red blood cells in the blood (Reticulocytosis)  
  • Increased spleen size (Splenomegaly) 
  • Accumulation of bilirubin, a breakdown product of haemoglobin (Unconjugated hyperbilirubinemia) 

30%-79% of people have these symptoms 

  • Haemolytic anaemia which is apparent at birth 
  • Iron overload (reflected by elevated serum ferritin) 
  • Prolonged yellowing of skin in new-born (Prolonged neonatal jaundice) 

5%-29% of people have these symptoms 

  • Unequal size of red blood cells (Anisocytosis)  
  • The foetus not growing as much as they should (Prenatal growth deficiency) 

How is it diagnosed?

A physical examination that reveals an enlarged spleen in the presence of jaundice is usually enough to call for further investigations. Blood tests are carried out. These blood tests will look for associated symptoms, such as the number of red blood cells, increase in immature red blood cells. 

DNA analysis should be ordered to confirm the diagnosis. 

Can it be treated?

Mild cases require no treatment. If you have severe anaemia, you may need blood transfusionsIn new-borns with dangerous levels of jaundice, a health care provider may recommend a blood transfusion, where you will have some of your blood removed and you will receive a blood transfusion high in red blood cells (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 for as long as possible to allow their immune system to mature. This procedure also requires long term follow up care including regular pneumococcal vaccinations and preventive antibiotics until age 5. In very severe cases, stem cell transplantation may be applicable. 

Do my family need to be tested?

Pyruvate kinase deficiency can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. If the child only inherits one copy of the faulty gene, they’ll be a carrier of the condition but won’t have the condition. 

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have. 

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Relevant Organisations

References

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