Pyruvate Kinase (PK) Deficiency | Symptoms & Causes

What are the symptoms of pyruvate kinase deficiency?

In pyruvate kinase (PK) deficiency red blood cells break apart more easily (hemolysis), causing hemolytic anemia. At birth, some infants may have significant anemia and severe jaundice, which is yellowing of the skin and the whites of the eyes (scleral icterus).  Other infants may have symptoms of anemia, such as poor in utero growth, before they are born. Children with PK deficiency may look pale, feel tired, or lack energy. They may also have yellowing of the whites of the eyes and skin, in addition to dark urine. Some children with PK deficiency have a lot of symptoms, and others have none.

Enlarged spleen

Affected children can also develop an enlarged spleen (splenomegaly). One function of the spleen is to filter red blood cells. The spleen becomes enlarged because it filters out the abnormal red blood cells. An enlarged spleen does not typically cause pain.

Hemolysis

Hemolytic episodes develop in the presence of stressors or triggers of hemolysis, which most often are infections and, therefore, more frequent in childhood. During these episodes, a child’s symptoms worsen, such as fatigue, paleness, scleral icterus, jaundice and/or dark urine.  An aplastic crisis is caused by parvovirus B19 infection (also called Fifth disease). This commonly causes a high fever and facial rash. Aplastic crises in individuals with PK deficiency often require a blood transfusion.

Iron overload

Iron overload is one of the most common findings in patients with PK deficiency.  Iron overload can occur both in individuals who receive blood transfusions and in those who have never been transfused. Iron overload is the abnormal accumulation of iron in various organs of the body, most commonly in the liver.  Iron loading is not associated with symptoms until a significant amount of iron is deposited, so it is important to monitor iron studies in individuals with PK deficiency.

Other complications

Other complications can occur in PK deficiency.  Children and adults with PK deficiency can develop gallstones.  Adolescents and adults can have weakened bones with an increased risk of bone fractures. Adults can develop skin sores (ulcers), typically around the ankles.  Other less common complications include high blood pressure in the arteries in the lungs and the right side of the heart (pulmonary hypertension) and blood cell production outside of the bone marrow (extramedullary hematopoiesis).

What causes PK deficiency?

Everyone inherits two copies of the PKLR gene, one from each of their parents. To inherit PK deficiency two non-working copies of the PKLR gene must be present. This is called an autosomal recessive genetic disease. People who inherit only one non-working copy of the PKLR gene (from one parent) do not have symptoms of hemolysis or anemia but are known as carriers of PK deficiency.

The PKLR gene provides instructions to produce two types of pyruvate kinase, one found in red blood cells and one found in liver cells. The liver is able to compensate for non-working PKLR genes, whereas the red blood cells are not. 

Over 300 different mutations of the PKLR gene have been identified. Most people inherit a different PKLR mutation from each of their parents. Many PKLR gene mutations are very rare, occurring only once.  Currently, approximately 25% of people diagnosed with PK deficiency have a newly described genetic mutation.