Welcome to the third part of our series, inspired by our patient guide, where we take a closer look at this condition ” Fast Facts for Patients and Supporters: PK Deficiency“, which is available for free on the internet. This article will explain the way that a deficiency in pyruvate kinase impacts you or your child.
The symptoms and challenges you or your child experience with PK deficiency may be very different from others, as the condition varies from person to person. The range of hemolytic anemia triggered by PK deficiency is usually mild to extreme with a normal hemoglobin concentration of 6-12 g/dL. Normal hemoglobin levels for healthy people differ by gender and age with a range of 10.5-16 g/dL.
Can You Predict Symptom Severity?
Patients and doctors often wonder if there are any early lab tests or signs that might help predict symptoms, or whether treatments like a transplant or splenectomy might eventually be needed. Researchers are actively exploring these questions to find clearer answers.
So far, research hasn’t found a clear link between pyruvate kinase (PK) enzyme activity and the severity of hemolysis. One possible reason is that the most affected red blood cells may be destroyed before the enzyme activity can even be measured—meaning your test results likely reflect the healthiest, most PK-sufficient cells. Individuals with more unstable PKLR gene mutations may be more likely to experience complications.
People who have lower levels of hemoglobin have more chances of suffering from complications. But, anyone suffering from PKD anemia could be prone to the problems described below.
Jaundice/Scleral Icterus
Due to PK deficiency, there’s a chance you might experience noticeable yellowing of the eyes and skin—known as jaundice. These symptoms can appear at any time, but they’re more likely to show up during periods of illness, dehydration, or stress.
Although spleen (splenectomy) removal helps in improving anemia for the majority of people suffering from PK deficiency, it will not solve the problem of scleral icterus or jaundice, since the hemolytic process is still in place after the splenectomy.
Why Do Some People Have More Jaundice than Others?
The severity of jaundice or scleral inflammation is related to the total unconjugated bilirubin levels.
People with Gilbert syndrome have an inherited genetic variation (two copies of a gene that doesn’t function properly), which affects the liver’s ability to process bilirubin. Gilbert syndrome is quite common—affecting up to 15% of the general population—so someone can have both PK deficiency and Gilbert syndrome at the same time. Those with Gilbert syndrome often notice more pronounced jaundice symptoms, especially during puberty.
Splenomegaly
The spleen may increase in size (a condition called splenomegaly) due to the increased destruction of red blood cells within the organ. This may happen during hemolytic episodes or in response to viral infections. It might happen in PK deficiency, having a spleen of normal size doesn’t rule out the condition—or the possibility that red blood cells are still breaking down more quickly than usual in the spleen. In cases of severe anemia, removing the spleen (splenectomy) may help improve symptoms.
An enlarged spleen can act like a sponge, trapping transfused red blood cells along with platelets and white blood cells, which can lead to lower blood counts.
Hemolytic Episodes
The occurrence of hemolytic crises or episodes due to stressors, or triggers for hemolysis. Pregnancy is also an important trigger for hemolysis.
In these instances, it is possible that your normal symptoms, like paleness, fatigue, and jaundice, as well as scleral icterus or dark urine, getting more severe. The spleen may increase in size. Blood tests will reveal:
- decreased hemoglobin/hematocrit
- Increased reticulocyte count
- an increase in the bilirubin
- an increase in lactate dehydrogenase (a sign of the breakdown of red blood cells in blood vessels).
Aplastic Crisis
This common viral infection usually causes high fever and facial rashes.
For people suffering from PK deficiency parvovirus infection reduces hemoglobin levels and stops or reduces the production of reticulocytes within the bone marrow.
This condition occurs only once in a lifetime and resolves on its own, much like other viral illnesses. Antibody tests for parvovirus can help determine whether there is a current infection or if you’ve had one in the past, indicating some level of immunity.
For PK insufficient, the aplastic crisis typically needs blood transfusions.
Gallstones
Contrary to the dietary-related gallstones that are common in middle-aged people it is possible to develop color-changed (bilirubin) gallstones at any time.
Some people with gallstones may not have any symptoms, while others might feel nausea or abdominal discomfort after eating. In some cases, gallstones can become lodged in the organs or ducts involved in bile production and storage (the biliary system), which can cause severe jaundice. Families managing family pyruvate kinase deficiency should be aware that this is a lifelong risk—even after a splenectomy.
Extramedullary Hematopoiesis
When your body needs to produce an unusually high number of red blood cells each day, blood cell production (called hematopoiesis) can start occurring outside the bone marrow—in organs like the spleen, liver, or even around the spine and chest.
Extramedullary hematopoiesis isn’t a common complication of PK deficiency, but it does happen in some cases.
Low Bone Density
Low bone density is another possible complication of PK deficiency. While the exact cause isn’t fully understood, it may be related to the bone marrow’s increased effort to produce red blood cells. Paying attention to your calcium and vitamin D intake may help support bone health
Infrequent Complications
Pulmonary hypertension—high blood pressure in the arteries of the lungs and the left side of the heart—is a known complication of PK deficiency. It’s often detected through routine screening or may become apparent when anemia cause swelling symptoms like fatigue and shortness of breath. Some individuals with PK deficiency may also develop leg ulcers, though the exact cause isn’t fully understood.
There may be other, less common symptoms as well, so it’s important to consult your doctor about any concerns or changes you’re experiencing.
Psychological Problems
Chronic anemia and the treatments for PK deficiency can sometimes affect your mental health. If you’re feeling depressed, having trouble sleeping or noticing mood swings, be sure to talk to your doctor.
Final Thoughts
Living with PK deficiency can be challenging, but being informed and aware of the symptoms can lead to better treatment. Regular medical care can help manage the condition effectively and improve long-term health outcomes for both children and their families.