Pyruvate kinase deficiency

Definition

Pyruvate kinase deficiency is an inherited deficiency 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

Pyruvate kinase deficiency is transmitted as an autosomal recessive trait, which means that a child must get the defective 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, followingG-6-PD deficiency.

Pyruvate kinase deficiency may produce mild or severe hemolysis (red cell breakdown) and anemia. Problems may first appear in the newborn as prolonged jaundice and anemia. Older children may be pale (due to anemia), and have intermittent episodes of jaundice. Mild cases may escape detection until adulthood.

Although pyruvate kinase deficiency is found in people of all ethnic backgrounds, certain populations, such as the Amish, have a somewhat higher incidence.

Symptoms

• A family history of pyruvate kinase deficiency
• Pallor
• Jaundice
• A yellowing of the whites of the eyes (icterus)
• Fatigue, lethargy caused by anemia
• Recurrent gallstones

Exams and Tests

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

Tests include the following:

• CBC showing anemia with normocytic (normal size) red blood cells
• Macrocytosis (large red blood cells)
• Pyruvate kinase activity shows deficient levels of this enzyme in red blood cells
• High levels of bilirubin in the blood
• Low levels of haptoglobin in the blood
• Increased osmotic fragility or red blood cells may not be present
• High stool urobilinogen
• Genetic testing for mutation in the pyruvate kinase gene

Treatment

Blood transfusions may be needed for severe anemia. Removal of the spleen (splenectomy) may help to reduce the destruction of red blood cells; however, this should not necessarily be performed as it does not help in all cases. In newborns with dangerous levels of jaundice, an exchange transfusion is likely to be recommended.

If a splenectomy was done, the person should receive pneumococcal vaccine at recommended intervals, and should receive antibiotic prophylaxis until the age of five.

Outlook (Prognosis)

The outcome varies. Some people have few or no symptoms, others have severe symptoms. Treatment is usually successful in reducing the severity of symptoms.

Possible Complications

Gallstones, composed of bilirubin produced in excess during hemolytic anemia, are a common problem. Severe pneumococcal disease following splenectomy is a possible complication.

When to Contact a Medical Professional

See your health care provider if jaundice occurs at any time; this is a symptom of many severe illnesses.

See your health care provider if you have a family history of this disorder and are planning to have children.

Prevention

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

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