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G6PD deficiency
This deficiency can cause haemolytic anaemia, often triggered by certain foods, medications, or infections. While generally manageable, severe cases may require medical attention, and it affects millions worldwide.
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Overview
G6PD deficiency, or glucose-6-phosphate dehydrogenase deficiency, is a common inherited condition that impacts red blood cells. These cells, responsible for carrying oxygen throughout the body, rely on the G6PD enzyme to protect them from harmful oxidative stress [PMID:33671239]. Without enough of this enzyme, red blood cells become vulnerable and can break down prematurely, a process known as haemolysis.
This condition is particularly prevalent in certain parts of the world, including Africa, Asia, the Mediterranean, and the Middle East, often reflecting historical exposure to malaria where the deficiency may have offered some protection [PMID:33671239]. While many individuals with G6PD deficiency may not experience symptoms, others can develop haemolytic anaemia when exposed to specific triggers.
Symptoms & clinical features
Symptoms of G6PD deficiency typically arise during episodes of haemolysis, which can be triggered by various factors. These triggers include certain medications (like some antimalarials or sulphonamides), fava beans, and infections [PMID:33671239]. When haemolysis occurs, common signs can include fatigue, pallor (unusually pale skin), shortness of breath, and a rapid heart rate, all due to the resulting anaemia.
Another significant symptom is jaundice, characterised by yellowing of the skin and whites of the eyes, which occurs because of the increased breakdown of red blood cells. Dark urine is also sometimes observed. In severe cases, particularly in newborns, untreated jaundice can lead to serious neurological complications, highlighting the importance of early detection and management.
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Affected organs
G6PD deficiency primarily affects the red blood cells, which circulate throughout the bloodstream. The consequences of red blood cell breakdown are felt widely across the body. The liver and spleen are particularly involved, as they are responsible for removing damaged red blood cells and processing their byproducts, such as bilirubin, which causes jaundice.
Severe anaemia resulting from extensive haemolysis can put a strain on the heart, leading to symptoms like a rapid heartbeat. In newborns, high levels of bilirubin can cross the blood-brain barrier, potentially damaging the brain if not managed promptly.
Risks & severity
The severity of G6PD deficiency can vary widely, from mild or asymptomatic forms to severe types that cause chronic anaemia. The most common risk is acute haemolytic anaemia, which develops rapidly after exposure to specific triggers. These triggers can include certain drugs, infections, or consumption of fava beans (a condition sometimes called 'favism') [PMID:33671239].
For most individuals, avoiding triggers is sufficient to prevent symptoms. However, severe haemolytic crises may require hospitalisation and supportive treatments, such as blood transfusions. Newborns with G6PD deficiency are at increased risk of severe jaundice, which, if left untreated, can lead to permanent neurological damage. The exact prevalence of G6PD deficiency is not well established globally, but it is considered common in many populations.
Genetic causes
G6PD deficiency is caused by pathogenic changes in the G6PD gene. This gene provides instructions for making the enzyme glucose-6-phosphate dehydrogenase. This enzyme plays a crucial role in a metabolic pathway known as the pentose phosphate pathway, particularly important in red blood cells. It produces a molecule called NADPH, which helps protect red blood cells from oxidative damage [PMID:33671239].
When the G6PD gene has a pathogenic variant, the amount or function of the G6PD enzyme is reduced. Without sufficient active enzyme, red blood cells are poorly equipped to handle oxidative stress. This vulnerability leads to their premature destruction when exposed to oxidising agents, resulting in haemolytic anaemia and its associated symptoms.
- G6PD glucose-6-phosphate dehydrogenaseThe G6PD gene provides instructions for producing the enzyme glucose-6-phosphate dehydrogenase, which is crucial for protecting red blood cells from oxidative damage.
Inheritance pattern
G6PD deficiency is inherited in an X-linked recessive pattern. This means the G6PD gene is located on the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome.
In males, a pathogenic variant on their single X chromosome will usually result in the condition. Females, having two X chromosomes, generally need a pathogenic variant on both X chromosomes to be significantly affected. However, due to X-inactivation (where one X chromosome in each cell is randomly 'switched off'), some females who carry a pathogenic variant on one X chromosome can show symptoms, particularly if a high proportion of their cells inactivate the X chromosome carrying the healthy G6PD gene. Affected males can pass the variant to all of their daughters, who will be carriers, but not to their sons. Carrier females have a 50% chance of passing the variant to each child, regardless of sex; sons who inherit the variant will be affected, and daughters who inherit it will be carriers.
X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.
Diagnosis & testing
Diagnosis of G6PD deficiency typically begins with clinical suspicion if an individual presents with symptoms of haemolytic anaemia after exposure to a known trigger. Initial blood tests may show signs of anaemia and red blood cell breakdown. A specific blood test to measure the activity of the G6PD enzyme in red blood cells is the most common diagnostic method. It is important that this test is not performed immediately after a haemolytic crisis, as the enzyme levels may appear falsely normal due to the increased production of young, enzyme-rich red blood cells [PMID:33671239].
In the UK, genetic testing, identified by R-code R196 for G6PD deficiency, can confirm the diagnosis and identify the specific pathogenic variant in the G6PD gene. Such testing is typically requested by a clinical genetics specialist following a referral from a general practitioner or another specialist. Referral to a clinical genetics service is usually made through the NHS Genomic Medicine Service following initial clinical suspicion and/or biochemical testing. Genetic counselling is often offered alongside testing to explain the implications for the individual and their family.
Management & lifestyle
Managing G6PD deficiency primarily involves avoiding substances and situations that can trigger haemolysis. This includes steering clear of certain medications, notably some antimalarials, sulphonamides, and aspirin in high doses, and also foods such as fava beans. Individuals are usually provided with a list of substances to avoid. During periods of infection, careful monitoring is important as infections can also initiate a haemolytic crisis.
In cases where haemolysis occurs, supportive treatment may be necessary. This can include monitoring blood counts, ensuring adequate hydration, and, in severe instances of anaemia, blood transfusions. Newborns with G6PD deficiency who develop significant jaundice may require phototherapy or, in rare cases, exchange transfusions to prevent neurological complications [PMID:33671239]. Regular follow-up with a haematologist or paediatrician is often recommended to ensure effective long-term management.
UK care pathway
In the UK, individuals suspected of having G6PD deficiency would typically be referred by their GP to a specialist, such as a haematologist or paediatrician, for diagnosis. If biochemical tests indicate G6PD deficiency, referral to a clinical genetics service can be arranged. Genetic testing under R-code R196 can confirm the diagnosis and help in understanding the specific genetic cause. Genetic counsellors within the NHS Genomic Medicine Service provide essential support, explaining the inheritance pattern, implications for family members, and helping individuals make informed decisions about genetic testing and future planning. This integrated approach ensures comprehensive care for affected individuals and their families.
Frequently asked questions
What foods should someone with G6PD deficiency avoid?
The most important food to avoid is fava beans, which are well-known to trigger haemolytic crises in individuals with G6PD deficiency. Other foods typically do not pose a risk; however, it is always best to consult with a healthcare professional for a personalised dietary guide.
Can G6PD deficiency be cured?
G6PD deficiency is an inherited genetic condition, and there is currently no cure. However, it can be very effectively managed by avoiding triggers that cause red blood cell breakdown. Most individuals lead a normal life by understanding and managing their condition.
Is G6PD deficiency life-threatening?
For most people, G6PD deficiency is not life-threatening, especially if triggers are avoided. Severe haemolytic crises can be serious, particularly in newborns or if left untreated. With appropriate management and medical attention during crises, serious complications can often be prevented.
How does G6PD deficiency affect women?
Because G6PD deficiency is X-linked, women are often carriers and may not show symptoms, or have milder symptoms, if they have one healthy copy of the gene. However, some women can experience haemolytic crises similar to men, depending on how their X chromosomes are expressed in their red blood cells. Genetic counselling can help explain the specific risks for women in a family.
Can people with G6PD deficiency donate blood?
Generally, individuals with G6PD deficiency are advised not to donate blood. This is because their red blood cells are more fragile and may not function as effectively or survive as long after transfusion, potentially compromising the quality of the donated blood product for the recipient.