Fast Facts: Pyruvate Kinase Deficiency for Patients and Supporters

R. Grace

Description

Pyruvate kinase deficiency is a rare genetic disease that causes red blood cells to break apart. Despite an ever-growing understanding of the disease, it remains unfamiliar to many healthcare professionals, and the information available to patients is limited. This superbly illustrated workbook is designed to help patients equip themselves with the best information about their condition to improve the conversations they have about it with their doctors and nurses. Contents: • What is pyruvate kinase deficiency? • What causes PK deficiency? • How is PK deficiency diagnosed? • How will PK deficiency affect me or my child? • Treating PK deficiency • What sort of monitoring might I need? • Special situations • When should I see my doctor? • What can I do to help myself?

Informations

• Publié par: S. Karger AG
• Date de parution: 06 février 2019
• Nombre de lectures: 1
• EAN13: 9781910797921
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Contents
What is pyruvate kinase deficiency?
What causes PK deficiency?
How is PK deficiency diagnosed?
How will PK deficiency affect me or my child?
Treating PK deficiency
What sort of monitoring might I need?
Special situations
When should I see my doctor?
What can I do to help myself?
Useful resources
First, the facts ...

Pyruvate kinase deficiency is a rare genetic disease that causes red blood cells to break apart easily (hemolysis).
Some patients have no or few symptoms; others have severe hemolytic anemia (a low red blood cell count or low hemoglobin level) that needs treatment with regular red blood cell transfusions.
Hemolytic anemia is associated with complications that need monitoring, including the development of gallstones, iron overload and low bone density.
Common supportive treatments for pyruvate kinase deficiency include blood transfusions, removal of the spleen (splenectomy) and medications to remove excess iron from the blood (chelation therapy).
Research into new treatments for pyruvate kinase deficiency is very promising.

To get the best outcome, you must equip yourself with the best information possible and ask the right questions. The space throughout this booklet is for you and your doctors, nurses and family to use as you see fit to get the answers and support you need. Let this booklet help you get organized.

My main concerns
Make a note of anything you want to discuss with your doctor here ...
What is pyruvate kinase deficiency?
Pyruvate kinase (PK) deficiency is a rare genetic disease that affects red blood cells. Everyone who has PK deficiency is born with it, even if they are diagnosed later in life. To understand how PK deficiency affects you, you need an understanding of the role of healthy red blood cells and pyruvate kinase, and what happens to red blood cells in PK deficiency.
The role of red blood cells

Red blood cells have a flexible shape called a biconcave disc, which looks like a flattened sphere. This flexible shape allows the cells to squeeze through narrow blood vessels (capillaries) as they deliver oxygen to the body. Healthy red blood cells can squeeze through the smallest capillaries.
The role of pyruvate kinase
Red blood cells make energy by converting glucose (a sugar) into pyruvate (an important molecule in metabolism) and a high-energy molecule called adenosine triphosphate (ATP) in a multistep process called glycolysis.

Pyruvate kinase is an enzyme that makes the last step in this process happen. It converts a protein called phosphoenolpyruvate into pyruvate and ATP. Less pyruvate kinase results in less ATP, so red blood cells have less energy.

The energy generated by glycolysis helps healthy red blood cells to keep their normal shape, stay flexible and protect themselves from injury (oxidative damage). In people with a normal amount of pyruvate kinase, red blood cells can generate enough ATP to last an average of 120 days.
The breakdown of red blood cells
The breakdown of red blood cells is called hemolysis. Normally, after 120 days, red blood cells break down and are removed from the circulation by the spleen.

Red blood cells that do not have enough pyruvate kinase cannot make enough energy to hold their shape, and they break apart more easily than healthy red blood cells. Instead of lasting 120 days, PK-deficient red blood cells only last a few days to weeks.
The breakdown of red blood cells (hemolysis) causes hemolytic anemia (a low red blood cell count or low hemoglobin level) and jaundice (yellowing of the skin), which is caused by bilirubin, a substance released from red blood cells as they break down.
Replacement of red blood cells
In healthy individuals, the bone marrow makes enough young red blood cells (reticulocytes) to balance the old or damaged red blood cells that are removed from the circulation by the spleen. Reticulocytes usually make up 1-2% of all the circulating red blood cells. The bone marrow also makes more reticulocytes when PK-deficient red blood cells break down, but overall more red blood cells break apart than are made.
Reticulocytes require more energy in the form of ATP than older red blood cells but, unlike mature red blood cells, they can make energy through pathways other than glycolysis. Reticulocytes are therefore less reliant on normal levels of pyruvate kinase than mature red blood cells. However, these alternative pathways rely on the presence of oxygen. The capillaries in the spleen are low in oxygen, so when reticulocytes flow through the spleen the alternative energy pathways no longer function, and the reticulocytes become reliant on glycolysis for energy.
In this environment, PK-deficient reticulocytes cannot make enough ATP and become dehydrated. They are then quickly destroyed in the spleen and/or liver. If people with PK deficiency have their spleen removed surgically (splenectomy), the reticulocytes have enough oxygen to make energy through the alternative energy pathways and can last longer. This is why the reticulocyte count increases after splenectomy in patients with PK deficiency (see Splenectomy, pages 23-6 ).

My main concerns
Make a note here of anything you want to ask your doctor about PK deficiency ...
What else happens to glycolysis in PK deficiency?
Although the main problem in PK deficiency is the inadequate amount of ATP made at the end of glycolysis, without enough pyruvate kinase for glycolysis to work efficiently, products made earlier in the pathway build up.

2,3-DPG controls the release of oxygen from red blood cells to different parts of the body. As 2,3-DPG rises, more oxygen is released from hemoglobin into the tissues.
Normally, the amount of 2,3-DPG is tightly regulated so that the body receives the right amount of oxygen. In PK deficiency, the levels of 2,3-DPG rise and more oxygen is released from hemoglobin into the tissues. Because of this, people with PK deficiency may tolerate a lower hemoglobin level than people with other types of anemia in which 2,3-DPG is not elevated.

FAST TEST
What does pyruvate kinase help red blood cells to do?
a) Carry oxygen b) Make energy c) Break apart
Answer: b)
What causes PK deficiency?
The production of pyruvate kinase is controlled by a gene called PKLR, which is found on the long (q) arm of chromosome 1 at position 22 (1q22).

Ask your doctor