G6PDH deficiency

Glucose-6-phosphate dehydrogenase deficiency (G6PDH deficiency) is a genetic disorder that primarily affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. The condition is caused by mutations in the G6PD gene, leading to a reduction in the activity of the glucose-6-phosphate dehydrogenase enzyme. This enzyme plays a critical role in the Pentose Phosphate Pathway, a cellular process that helps protect red blood cells from damage caused by reactive oxygen species. Without sufficient G6PD activity, red blood cells can be prematurely destroyed in a process known as hemolysis, leading to hemolytic anemia.

Causes and Genetics

G6PDH deficiency is inherited in an X-linked recessive manner. The G6PD gene is located on the X chromosome, one of the two sex chromosomes. Males (who have one X and one Y chromosome) are more frequently affected because they have only one copy of the G6PD gene. Females (who have two X chromosomes) can be carriers of the condition; however, they are less likely to exhibit symptoms unless both copies of their G6PD gene are affected.

Symptoms

The severity of G6PDH deficiency symptoms can vary widely among affected individuals. Some people may be asymptomatic, while others can experience episodes of acute hemolytic anemia, particularly in response to certain triggers. Common triggers include infections, certain foods (such as fava beans), and a variety of medications (including some antibiotics and antimalarials). Symptoms of hemolytic anemia may include fatigue, shortness of breath, rapid heart rate, yellowing of the skin and eyes (jaundice), and dark urine.

Diagnosis

Diagnosis of G6PDH deficiency typically involves a combination of clinical evaluation, family history, and laboratory tests. The most commonly used laboratory test measures the activity of the G6PD enzyme in red blood cells. Genetic testing may also be performed to identify specific mutations in the G6PD gene.

Treatment and Management

There is no cure for G6PDH deficiency, but the condition can be managed by avoiding known triggers of hemolytic episodes. In cases where hemolytic anemia occurs, treatment focuses on supportive care, such as hydration and, in severe cases, blood transfusions. Individuals with G6PDH deficiency should be educated about the condition and its triggers to help prevent episodes of hemolysis.

Epidemiology

G6PDH deficiency is one of the most common enzyme deficiencies worldwide, affecting an estimated 400 million people. The prevalence of the condition varies significantly among different populations and regions, with higher rates observed in parts of Africa, the Mediterranean, the Middle East, and Asia. This geographic distribution is thought to be related to the protective effect of G6PDH deficiency against malaria, a disease endemic to these areas.

See Also

• Hemolytic anemia
• Pentose Phosphate Pathway
• X-linked recessive inheritance