Healthy red blood cells are produced in the bone marrow, and last for about 120 days. Oxygen in the lungs binds to a molecule in red blood cells called haemoglobin.
Health red blood cells have a flexible shape, which allows them to squeeze through narrow blood vessels (capillaries) as they deliver oxygen throughout the body.
Red blood cells that have decreased amounts of pyruvate kinase make less ATP, which means that they have less energy.
With less energy, the red blood cells cannot hold their shape, become less flexible, and break apart as they pass through the spleen and liver. When red blood cells break apart the so-called haemolysis occurs. Because of haemolysis, PK-deficient red blood cells only last for a few days or weeks.
The bone marrow continues to make new red blood cells, but these are particularly susceptible to breaking apart in the spleen. The overall result is too few red blood cells, a condition otherwise known as anaemia.
Pyruvate kinase deficiency is a type of haemolytic anaemia.
Yes. PK deficiency is an inherited autosomal recessive disease.
The production of the pyruvate kinase enzyme is controlled by a gene called PKLR, found on chromosome 1 at position 22.
To inherit the disease, you have to receive two copies of a non-working PKLR gene (one from each parent). This means that for every pregnancy by parents where both have one non-functional PKLR gene, there is a 25% chance that the child will have PK deficiency.
To investigate the cause of anaemia, doctors will take a blood sample to see if the patient has haemolytic anemia.
If haemolytic anaemia is confirmed, then further blood tests will be carried out to find the cause of the haemolytic anemia.
As PK deficiency is not consistently associated with any specific haematologic features diagnosis focuses on two diagnostic tests:
- Pyruvate kinase enzyme activity
- Genetic testing
Analysis of PK enzymatic activity is the standard for diagnostic testing. PK activities at the low end of normal in the context of normal/elevated levels of other glycolytic pathways enzymes are suggestive of PK deficiency.
Genetic testing can help confirm diagnosis in unclear cases, and should be considered if the patient:
- Has normal or decreased PK activity in the presence of elevated activity of other age dependent red cell enzymes
- Is chronically transfused
- Has low PK activity, but no family history of the disease
Signs and symptoms vary from person to person. Nevertheless, the most common symptoms are:
- Yellowing of the whites of the eyes (scleral icterus)
- Yellowing of the skin (jaundice) and/or pale skin
- Fatigue (and a lesser ability to perform physical activity)
- Excess iron increases the risk of liver, heart and hormone problems, and other complications
- Gallstones may cause abdominal pain, nausea and vomiting
- Enlarged spleen (splenomegaly)
- Low bone strength (osteopenia)
Less common signs and symptoms may occur, so ask your doctor about any problems you have.
For the time being there is no drug available to treat PK deficiency, but symptoms can be managed. The type of supportive treatment received depends on how the disease affects the patient.
Blood transfusions are given to lessen the symptoms of anaemia. They increase the haemoglobin level. Some patients may never need to have a transfusion. Some have only a few, and others have frequent transfusions.
Special circumstances that often require transfusions include:
- Hemolytic crisis – a worsening of hemolytic anemia caused by infections, stress or pregnancy.
- Aplastic crisis – a temporary halt in new red blood cell production caused by parvovirus infection (Fifths disease), which causes a temporary severe anemia and then self-resolves.
With or without blood transfusions, PK deficiency can lead to too much iron in the body.
Patients need regular monitoring for iron overload through blood tests (a ferritin test) or radiology scans. Iron overload can be treated with medications (chelation therapy) or blood draws (phlebotomy).
High levels of bilirubin cause jaundice (yellowing of the skin) in children and adults. Newborns can develop complications of the nervous system related to jaundice. Fluorescent light decreases bilirubin, so newborns are often treated with phototherapy. Or they may receive exchange transfusion in which an amount of blood is removed and replaced with transfused blood.
Removal of the spleen (splenectomy) increases haemoglobin levels in most patients with PK deficiency, improving anaemia and reducing the need for transfusions. Without a spleen, young red blood cells survive longer and the reticulocyte count increases.
After the spleen is removed the anaemia improves, but haemolysis continues.
The gallbladder may be removed (cholecystectomy) at the same time as the spleen or if you have gallstones that cause symptoms.
Removal of the spleen (splenectomy) increases haemoglobin levels in most patients with PK deficiency, improving anaemia and reducing the need for transfusions. Without a spleen, young red blood cells survive longer. After the spleen is removed the anaemia improves, but haemolysis continues.
Therefore, doctors may recommend:
- Regular antibiotics after surgery to prevent infection.
- Additional (non-routine) vaccinations before and after the operation.
- Medications after surgery to prevent blood clots.
The gallbladder may be removed (cholecystectomy) at the same time as the spleen to deal with existing or to prevent the development of gallstones.