A rare genetic disease that causes red blood cells to break down faster than they should is called pyruvate kinase deficiency (PK deficiency). It may also cause hemolytic anemia and the following symptoms. For example, extreme tiredness (fatigue), weakness, and a fast heart rate. In general, there are some treatments available that may help relieve the symptoms and improve your quality of life.
An enzyme required by red blood cells to produce energy and survive is called pyruvate kinase. If you do not have enough of these enzymes, it may lead to red blood cell breakdown before the body makes new ones. However, red blood cells carry oxygen to all tissues and organs in the body. When red blood cells are not enough, it often leads to anemia.
Moreover, this is a chronic disorder, which means you will need treatment for the rest of your life.
Symptoms
The symptoms of anemia are very similar to those caused by PK deficiency. Check below for the most common symptoms of anemia:
- Dyspnea (shortness of breath)
- Pale skin
- Headaches
- Dizziness
- Fast heartbeat
- Extreme tiredness (fatigue)
- Weakness
Sometimes, people may experience additional symptoms when the waste products that remain from destroyed red blood cells begin to build up in the body. For example, jaundice (yellowing of the eyes and skin), dark-colored urine, and an enlarged spleen.
Causes
This is an inherited genetic disorder related to the PKLR gene. The genes contain instructions that tell cells what to do. The PLKR gene is responsible for telling red blood cells how to make the enzyme pyruvate kinase. Therefore, this enzyme is used by the red blood cells to produce adenosine triphosphate (ATP), which is the primary energy source.
In people with PK deficiency, there is an error in the PKLR gene, which negatively affects red blood cells that produce pyruvate kinase and eventually ATP. Instead, red blood cells break down too quickly (hemolytic anemia).
Autosomal Recessive Inheritance
This condition often occurs when you get 2 abnormal genes, one from each biological parent (autosomal recessive inheritance). When you get only one abnormal PKLR gene from one parent, you become a carrier. It means the abnormal gene can be passed to your children in the future. In general, there is a 25% chance you will get the abnormal gene from your biological parents during pregnancy.
Risk Factors
While doctors do not fully understand what exactly causes this condition, they have identified some factors that may elevate your risk of developing it. This condition is diagnosed more commonly in some populations (such as northern European descent and some Amish communities in Pennsylvania and Ohio).
To reduce the risk of developing this condition, you can perform some genetic tests before pregnancy to make sure you do not have this abnormal gene. It is very important to understand the risks of having children with pyruvate kinase deficiency.
What Are The Possible Complications of Pyruvate Kinase Deficiency?
In some cases, this condition can cause mild symptoms as people do not realize they have a health condition. It often occurs until the following complications appear. Check some examples below:
- Pulmonary hypertension (high blood pressure in the lung arteries)
- Weakened bones (this complication increases your risk of osteoporosis and bone fractures)
- Pregnancy complications, including preterm birth and miscarriage
- Leg ulcers
- Iron overload
- Gallstones
- Aplastic crisis (a sudden worsening of anemia)
- Splenomegaly (enlarged spleen)
- Liver, heart, or bone diseases
- Blood clots
The previous list does not contain a full list of complications that may occur in people with PK deficiency. In any case, you can consult with your doctor about ways to reduce the risk of developing them. Furthermore, there is no way to prevent this condition because it occurs during pregnancy.
Diagnosis
Sometimes, doctors suspect PK deficiency during pregnancy on a prenatal ultrasound. Therefore, doctors may perform additional tests for this condition. One sign is fluid buildup in the baby’s body (hydrops fetalis). After birth, doctors may perform blood tests to check for the following conditions if your child has symptoms of PK deficiency. For example:
- Anemia – Doctors will check for hemolytic anemia, which indicates PK deficiency. However, there are multiple health conditions that may cause anemia, and doctors perform blood tests to exclude them.
- Decreased pyruvate kinase activity – Some biochemical tests may measure how active your pyruvate kinase enzymes are.
- The PKLR gene mutation – Doctors may also perform genetic tests that require a blood sample. They will check for the abnormal PKLR gene that causes this condition.
Treatment
The treatment can be different in people with PK deficiency because it depends on when you are diagnosed and how severe the symptoms are.
Fetuses and Newborns
Doctors often recommend the following treatment options for infants and newborns with PK deficiency. For example:
- Intrauterine fetal transfusion – This test involves injecting red blood cells from a donor into the fetus. It helps prevent and improve anemia and relieve symptoms.
- Phototherapy – This test helps newborns break down bilirubin. It is a waste product of destroyed red blood cells. If bilirubin begins to build up in the body, it may lead to jaundice (yellowing of the eyes and skin).
- Exchange transfusion – This option is often recommended in more severe cases where babies need a blood transfusion.
Children and Adults
- Blood transfusions – Usually, people with PK deficiency need this treatment for the rest of their lives. It helps increase red blood cell count.
- Mitapivat – This is a medicine used to treat PK deficiency and hemolytic anemia in adults. It was approved by the FDA (Food and Drug Administration) in 2022.
- Folic acid supplements – This supplement is used to help the body produce new red blood cells. It is usually recommended by doctors when you do not get enough folic acid from your diet.
- Iron chelation – Iron may begin to build up in the body when there is too much. It often occurs due to regular blood transfusions. That’s why doctors often recommend Iron chelation to get rid of excessive Iron.
- Spleen removal – The spleen stores destroyed red blood cells. That’s why it may become enlarged over time.
- Gallbladder removal – Sometimes, people develop gallstones. In such cases, doctors may recommend removing the gallbladder.
Currently, healthcare professionals are testing some treatments that may help improve the condition. These include:
- Stem cell transplant – During this procedure, surgeons will replace your stem cells. New stem cell comes from a donor.
- Gene therapy – This treatment helps replace the abnormal genes with healthy ones.
Frequently Asked Questions
When should I see my healthcare provider?
People with PK deficiency often need regular checkups for the rest of their lives. For more details, discuss it with your doctor.
What is the life expectancy of someone with pyruvate kinase deficiency?
The survival rate for people over 55 years of age is between 86% and 92%. However, it may significantly decrease if you develop complications.
Can pyruvate kinase deficiency be cured?
No, this condition can be managed only. Doctors often recommend different treatment options to relieve the symptoms and improve your quality of life. However, researchers are now testing some treatments with curative potential. These include stem cell transplant and gene therapy. If you have any other questions, ask your healthcare provider.
