Pyruvate Kinase Deficiency

Pyruvate kinase (pronounced “pie-ROO-vate KYE-nace”) deficiency is a rare genetic disorder that causes your red blood cells to break down too fast. Pyruvate kinase is an enzyme that your red blood cells need to make energy and survive. When you don’t have enough of it (deficiency), your red blood cells break down before your body can make new ones to replace them.

Your red blood cells carry oxygen throughout your body. Having too few red blood cells because of a pyruvate kinase deficiency means your body’s other cells may not get enough oxygen. As a result, you may have symptoms of anemia.

Pyruvate kinase (PK) deficiency is a condition you’re born with that lasts forever. This means you’ll need lifelong care from a hematologist (blood doctor). But symptoms vary from person to person.

Symptoms of pyruvate kinase deficiency

Anemia symptoms are common with PK deficiency. They include:

• Fatigue (weakness and extreme tiredness)
• Rapid heartbeat
• Shortness of breath
• Pale skin
• Dizziness
• Headaches

Other signs of PK deficiency happen when the waste products from destroyed red blood cells build up in your body. Signs include:

• Jaundice (yellowish skin and yellow whites of your eyes)
• An enlarged spleen
• Dark-colored pee (urine)

What is the age of onset for pyruvate kinase deficiency?

A PK deficiency is present at birth. But the timing when symptoms become noticeable depends on how severe your condition is.

For instance, newborns with noticeable symptoms often need lifesaving treatment. Infants may be fussy and have trouble feeding, while children may have low energy. Adults may not notice symptoms until a health event stresses their body. Examples include pregnancy, an infection or injury.

Pyruvate kinase deficiency causes

Pyruvate kinase deficiency is an inherited genetic disorder related to the PKLR gene. Think of your genes as the instructions that tell your cells what to do. Your PKLR gene tells your red blood cells how to make the enzyme pyruvate kinase. Pyruvate kinase helps your red blood cells make adenosine triphosphate (ATP), which is their primary energy source.

With PK deficiency, a variation (error) in your PKLR gene prevents your red blood cells from making enough pyruvate kinase. As a result, your red blood cells can’t make the ATP they need to thrive. Instead, they break down too soon, leaving you with low red blood cells. This is called hemolytic anemia.

Autosomal recessive inheritance

You have to inherit two faulty PKLR genes to have PK deficiency. You inherit one from each biological parent. This is called autosomal recessive inheritance. Each parent has one normal PKLR gene and one faulty PKLR gene. Unless they’ve received genetic testing, they won’t know that they carry a faulty PKLR gene that they can pass along to their children.

There’s a 1 in 4 (25%) chance that both parents will pass the faulty PKLR gene to their child, causing a pyruvate kinase deficiency.

Risk factors

Since PK deficiency is passed from parents to their biological children, it affects some populations more than others. Healthcare providers most commonly diagnose it in people of northern European descent. It’s more widespread in certain Amish communities in Pennsylvania and Ohio.

How to lower your risk

You can’t prevent conditions you inherit. But you can check your risk of having a child with a pyruvate kinase deficiency. If you or your partner has a family history of this disorder, it may be a good idea to speak with a genetics counselor. They can explain DNA tests that may be available. They can walk you through possible outcomes during pregnancy.

Complications of this condition

Some people don’t realize they have a pyruvate kinase deficiency until they develop complications, like:

• Gallstones
• Iron overload
• Leg ulcers
• Pulmonary hypertension
• Weakened bones (which increase your risk of broken bones and osteoporosis in older age)
• Pregnancy complications, including miscarriage and preterm birth

Pregnancy can stress your body in ways that may trigger or intensify PK deficiency symptoms. This can impact the fetus. But pregnancy complications are rare. If you’re pregnant, your pregnancy providers will work with your hematologist to keep you and the fetus safe.

How doctors diagnose this condition

Signs of pyruvate kinase deficiency in a fetus may show up during a prenatal ultrasound. If your pregnancy care provider sees warning signs, they may test for pyruvate kinase deficiency. One sign is fluid buildup in the fetus’s body (hydrops fetalis).

If you or your child experiences symptoms of PK deficiency, a healthcare provider will order blood tests. These tests will check for:

• Anemia. Your provider will see if you have hemolytic anemia. Lots of conditions can cause anemia. Blood tests will help your provider rule those out.
• Reduced pyruvate kinase activity. Biochemical tests can measure how active your pyruvate kinase enzyme is. It’s less active with pyruvate kinase deficiency.
• The PKLR gene mutation. Molecular tests can find errors in the PKLR gene that cause the disorder.

How is pyruvate kinase deficiency treated?

Treatment depends on how severe your symptoms are and when you’re diagnosed.

Fetuses and newborns

Fetuses and newborns with pyruvate kinase deficiency may need lifesaving transfusions and treatments, like:

• Intrauterine fetal transfusion. A fetus with PK deficiency may need treatment before birth. A healthcare provider injects red blood cells from a donor into the fetus during this procedure.
• Phototherapy. Phototherapy helps your newborn’s body break down bilirubin. Bilirubin is a waste product of destroyed red blood cells. Too much of it can cause jaundice.
• Exchange transfusion. Newborns with severe jaundice may need an exchange transfusion. Their provider will replace their blood with a donor’s blood.

Infants, children and adults

Treatments can manage anemia symptoms and prevent complications of PK deficiency. They include:

• Blood transfusions. You may need lifelong blood transfusions to boost your low red blood cells. Some people who need regular transfusions as children find they no longer need them as adults.
• Mitapivat (Pyrukynd®). This medicine treats pyruvate kinase deficiency and hemolytic anemia in adults. The U.S. Food and Drug Administration (FDA) approved it in 2022.
• Folic acid supplements. Folic acid helps your body make red blood cells. You may need to take supplements if you’re not getting enough from the foods you eat.
• Iron chelation. Too much iron may build up in your body. It can happen because of the condition itself or from regular blood transfusions. Iron chelation gets rid of excess iron.
• Spleen removal. Your spleen stores destroyed red blood cells. It may get too big if you have a pyruvate kinase deficiency. If this happens, a provider may need to remove it.
• Gallbladder removal. You may develop gallstones with a pyruvate kinase deficiency. If they cause problems, your provider may recommend removing your gallbladder.

Researchers are testing new treatments, including:

• Stem cell transplant. During this procedure, you receive stem cells from a donor that eventually mature into healthy red blood cells.
• Gene therapy. Your healthcare provider replaces the faulty gene that causes pyruvate kinase deficiency with a healthy gene.

When should I see my healthcare provider?

You’ll need regular checkups with your hematologist to check your red blood cell levels. They’ll also test for complications, like too much iron in your body.

They’ll let you know the follow-up care you need based on your condition.

What can I expect if I have this condition?

Your experience depends on your symptoms and treatments. Potential complications of a PK deficiency shape your experience, too. Also, your experience can change over your lifetime. For example, children who need regular blood transfusions may not need them as adults. An adult may not realize there’s an issue until a major health event triggers symptoms.

Your healthcare provider is your best resource for explaining what a pyruvate kinase deficiency means for your long-term health.