Phosphoglycerate kinase 1 deficiency

Phosphoglycerate Kinase 1 Deficiency (PGK1 Deficiency) is a rare genetic disorder characterized by a deficiency in the enzyme phosphoglycerate kinase (PGK), which plays a crucial role in the glycolysis pathway. This condition is inherited in an X-linked recessive manner, affecting mainly males, though female carriers may exhibit some symptoms due to X-chromosome inactivation.

Overview

Phosphoglycerate kinase 1 (PGK1) is an enzyme essential for the glycolytic pathway, which is the primary process for the production of adenosine triphosphate (ATP) in cells. ATP serves as a universal energy currency in cells, supporting various biological functions. PGK1 catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, generating one molecule of ATP in the process. Deficiency in PGK1 disrupts this pathway, leading to reduced ATP production and accumulation of glycolytic intermediates, which can affect multiple organ systems.

Symptoms

The clinical presentation of PGK1 Deficiency can vary widely among affected individuals. Common symptoms include:

• Hemolytic anemia - premature destruction of red blood cells, leading to fatigue, pallor, and jaundice.
• Myopathy - muscle weakness and cramps, particularly after exercise.
• Central nervous system involvement - seizures, intellectual disability, and stroke-like episodes in some cases.
• Neutropenia - a decrease in neutrophils, increasing susceptibility to infections.

Diagnosis

Diagnosis of PGK1 Deficiency involves a combination of clinical evaluation, family history, and laboratory tests. Specific tests may include:

• Enzyme assay - measuring the activity of PGK in red blood cells.
• Molecular genetic testing - identifying mutations in the PGK1 gene.

Treatment

There is no cure for PGK1 Deficiency, and treatment is symptomatic and supportive. Management strategies may include:

• Blood transfusions for severe anemia.
• Anticonvulsant medication for seizure control.
• Physical therapy to manage myopathy.
• Preventive measures for infections due to neutropenia.

Genetics

PGK1 Deficiency is caused by mutations in the PGK1 gene located on the X chromosome (Xq13). As an X-linked recessive disorder, males are primarily affected, while females can be carriers. Female carriers may exhibit symptoms due to skewed X-chromosome inactivation.

Epidemiology

PGK1 Deficiency is extremely rare, with only a few dozen cases reported in the medical literature worldwide. The exact prevalence is unknown.

See Also

• Glycolysis
• X-linked recessive inheritance
• Hemolytic anemia
• Myopathy

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