About phosphoglycerate kinase deficiency

What is phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency is an extremely rare inherited metabolic disorder characterized by deficiency of the enzyme phosphoglycerate kinase. This enzyme is essential for the breakdown of glycogen, resulting in the release of energy. Symptoms and findings associated with the disorder may include low levels of circulating red blood cells (hemolytic anemia); varying degrees of intellectual disability; rapidly changing emotions (emotional lability); an impaired ability to communicate through and/or to comprehend speech or writing (aphasia); exercise-induced pain, stiffness, or cramps; enlargement of the spleen (splenomegaly); and/or paralysis of one side of the body (hemiplegia). In most cases, phosphoglycerate kinase deficiency is inherited as an X-linked genetic trait. In such cases, the disorder is fully expressed in males only; however, some females who carry one copy of the disease gene (heterozygotes) may have hemolytic anemia.

What are the symptoms for phosphoglycerate kinase deficiency?

Tachycardia symptom was found in the phosphoglycerate kinase deficiency condition

The three main features of phosphoglycerate kinase deficiency are hemolytic anemia, intellectual disability, and muscle problems (myopathy). An individual with the disorder may be affected by one or more of these features, but it is unusual for one person to exhibit all three signs.

Individuals with childhood PGK deficiency have some degree of Intellectual disability with delayed language acquisition. Some have epilepsy and strokes.

Most adult patients are moderately affected, and heterozygous females may show only mild hemolytic anemia with no myopathy or intellectual disability.

Myopathy with exercise-induced stiffness, cramps, and muscle Pain is seen in adolescents and young adult males. The cramps are often severe and may incapacitate the individual for hours. Myoglobinuria is often seen in severe episodes.

What are the causes for phosphoglycerate kinase deficiency?

PGK is considered to be an inborn error of metabolism that is inherited in an X-linked manner. The gene responsible is located on the X chromosome (Xq13).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome Xq13” refers to band 13 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males.  Females that have a defective gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the defective gene.  Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the defective gene to all of his daughters who will be carriers.  A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

What are the treatments for phosphoglycerate kinase deficiency?

Treatment of phosphoglycerate kinase deficiency may consist of iron supplements and blood transfusions when needed. The avoidance of strenuous exercise when evidence that muscle breakdown has taken place is very important and special care is needed during neurologic crisis to avoid life-threatening situations. Bone marrow transplantation may be an option in cases with severe neurological deterioration.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

What are the risk factors for phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase, which affects the survival of red blood cells, causing anemia.


  • Pyruvate kinase deficiency is due to a mutation in the PKLR gene. There are four pyruvate kinase isoenzymes, two of which are encoded by the PKLR.
  • Mutations in the PKLR gene, therefore, cause a deficiency in the pyruvate kinase enzyme.

Risk factors:

  • Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive.
  • Pyruvate kinase deficiency is the second most common cause of enzyme-deficient anemia following G6PD deficiency.
  • Pyruvate kinase deficiency is most commonly an autosomal recessive trait. Although it is mostly homozygotes that demonstrate symptoms of the disorder, compound heterozygotes can also show clinical signs.
  • Since it is an autosomal recessive disease, it affects male infants more than females.
  • Severe conditions of the disease cause death of the fetus even before birth.
  • Pyruvate kinase deficiency happens worldwide; however northern Europe and Japan have many cases.
  • The prevalence of pyruvate kinase deficiency is around 51 cases per million in the global population.
  • The disease has practically no cure, except for frequent blood transfusions or a bone marrow transplant.

Mild to severe hemolytic Anemia,Cholecystolithiasis,Tachycardia,Hemochromatosis
Blood transfusion,Bone marrow transpalant,Mitapivat
Anemia,Fatigue,Pain in the lower abdomen

Is there a cure/medications for phosphoglycerate kinase deficiency?

Phosphoglycerate kinase deficiency is due to a mutation in the PKLR gene. It causes severe hemolytic anemia in babies and young children.


  • More often, the less severe forms do not need any treatment.
  • A fetus with a severe form of this disease tends to die within the mother’s womb even before birth.
  • If the patient shows the same sign after birth, treatment is the only option. The treatment is usually symptomatic. It is focused on reducing the severity of the symptoms.
  • The underlying cause of the disease cannot be cured as it is a genetic condition.
  • The most common treatment preferred is blood transfusion; it is done in both infants and adults. This is done when the red blood cell level falls below a critical level
  • Bone marrow transplant is another treatment option for young patients.
  • There is a natural way the body tries to treat this disease. It increases erythrocyte production (reticulocytosis) because reticulocytes are immature red blood cells that still contain mitochondria and so can produce ATP via oxidative phosphorylation.
  • Therefore, a treatment option in extremely severe cases is to perform a splenectomy.
  • This does not stop the destruction of erythrocytes, but it does help increase the number of reticulocytes in the body since most hemolysis occurs when the reticulocytes are trapped in the hypoxic environment of the spleen.
  • This reduces severe anemia and the need for blood transfusions.

Mild to severe hemolytic Anemia,Cholecystolithiasis,Tachycardia,Hemochromatosis
Blood transfusion,Bone marrow transpalant,Mitapivat
Anemia,Fatigue,Pain in the lower abdomen

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