Pyruvate kinase deficiency

Answer 1

Definition

Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Without this enzyme, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia).

Causes, incidence, and risk factors

Pyruvate kinase deficiency is passed down as an autosomal recessive trait. A child must receive the non-working gene from both parents to develop the disorder.

There are many different types of enzyme-related defects of the red blood cell that can cause hemolytic anemia. Pyruvate kinase deficiency is the second most common cause, after G-6-PD deficiency.

Pyruvate kinase deficiency is found in people of all ethnic backgrounds. However, certain populations, such as the Amish, are somewhat more likely to develop the condition.

Symptoms

• Anemia
• A yellowing of the whites of the eyes (icterus)
• Fatigue, lethargy
• Jaundice
• Pale skin (pallor)

Signs and tests

During a physical exam, the doctor will look for an enlarged spleen.

Tests include the following:

• Bilirubin in the blood
• CBC
• Genetic testing for mutation in the pyruvate kinase gene
• Large red blood cells (macrocytosis)
• Levels of haptoglobin in the blood
• Osmotic fragility
• Pyruvate kinaseactivity
• Stool urobilinogen

Treatment

People with severe anemia may need blood transfusions. Removing the spleen (splenectomy) may help reduce the destruction of red blood cells. However, this does not help in all cases. In newborns with dangerous levels of jaundice, the health care provider may recommend an exchange transfusion.

Someone who had a splenectomy should receive the pneumococcal vaccine at recommended intervals. They also should receive preventive antibiotics until age 5.

Expectations (prognosis)

The outcome varies. Some people have few or no symptoms. Others have severe symptoms. Treatment can usually make symptoms less severe.

Complications

Gallstones are a common problem. They are made of too much bilirubin, which is produced during hemolytic anemia. Severe pneumococcal disease is a possible complication after splenectomy.

Calling your health care provider

See your health care provider if:

• You have jaundice (this is a symptom of many severe illnesses)
• You have a family history of this disorder and are planning to have children

Prevention

Genetic counseling can help prospective parents with a family history of pyruvate kinase deficiency. People who carry the gene can often be diagnosed by finding decreased RBC pyruvate kinase activity in their red blood cells.

References

Segel GB. Enzymatic defects. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 463.

Answer 2

Definition

Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Without this enzyme, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia).

Causes, incidence, and risk factors

Pyruvate kinase deficiency is passed down as an autosomal recessive trait. A child must receive the non-working gene from both parents to develop the disorder.

There are many different types of enzyme-related defects of the red blood cell that can cause hemolytic anemia. Pyruvate kinase deficiency is the second most common cause, after G-6-PD deficiency.

Pyruvate kinase deficiency is found in people of all ethnic backgrounds. However, certain populations, such as the Amish, are somewhat more likely to develop the condition.

Symptoms

• Anemia
• A yellowing of the whites of the eyes (icterus)
• Fatigue, lethargy
• Jaundice
• Pale skin (pallor)

Signs and tests

During a physical exam, the doctor will look for an enlarged spleen.

Tests include the following:

• Bilirubin in the blood
• CBC
• Genetic testing for mutation in the pyruvate kinase gene
• Large red blood cells (macrocytosis)
• Levels of haptoglobin in the blood
• Osmotic fragility
• Pyruvate kinaseactivity
• Stool urobilinogen

Treatment

People with severe anemia may need blood transfusions. Removing the spleen (splenectomy) may help reduce the destruction of red blood cells. However, this does not help in all cases. In newborns with dangerous levels of jaundice, the health care provider may recommend an exchange transfusion.

Someone who had a splenectomy should receive the pneumococcal vaccine at recommended intervals. They also should receive preventive antibiotics until age 5.

Expectations (prognosis)

The outcome varies. Some people have few or no symptoms. Others have severe symptoms. Treatment can usually make symptoms less severe.

Complications

Gallstones are a common problem. They are made of too much bilirubin, which is produced during hemolytic anemia. Severe pneumococcal disease is a possible complication after splenectomy.

Calling your health care provider

See your health care provider if:

• You have jaundice (this is a symptom of many severe illnesses)
• You have a family history of this disorder and are planning to have children

Prevention

Genetic counseling can help prospective parents with a family history of pyruvate kinase deficiency. People who carry the gene can often be diagnosed by finding decreased RBC pyruvate kinase activity in their red blood cells.

References

Segel GB. Enzymatic defects. In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 457.

Reviewed By

Review Date: 02/02/2012

Chad Haldeman-Englert, MD, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.