What is Glucose-6-Phosphate Dehydrogenase Deficiency?
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme, a type of protein that helps our body to function correctly, that we all have in our cells. This enzyme plays an important role in protecting our cells from harmful molecules called reactive oxygen species (ROS). It does this by providing other substances that help defend against damage from ROS.
Red blood cells, which carry oxygen around our body, are especially at risk from ROS because they can’t replace damaged proteins. When someone inherits a G6PD deficiency, it means they have fewer of these protective enzymes, which can lead to a condition called acute hemolytic anemia if there’s a spike in ROS.
This spike in ROS could be triggered by stress, eating foods like fava beans that have high levels of substances that promote oxidation (a kind of cell damage), or certain medicines. Anti-malarial drugs are particularly known to spark off hemolytic anemia in people with a G6PD deficiency.
Below is a list of common medications in the US which have been associated with triggering a hemolytic crisis in those with a G6PD deficiency. These should be avoided or used carefully if you have this enzyme deficiency:
Acetaminophen, Acetylsalicylic acid, Chloramphenicol, Chloroquine, Colchicine, Diaminodiphenyl sulfone, Diphenhydramine, Glyburide, Isoniazid, L-Dopa, Methylene blue, Nitrofurantoin, Phenazopyridine, Primaquine, Rasburicase, Streptomycin, Sulfacetamide, Sulfanilamide, Sulfapyridine, Sulfacytine, Sulfadiazine, Sulfaguanidine, Sulfamethoxazole, Sulfisoxazole, Trimethoprim, Tripelennamine, Vitamin K.
For a more extensive list, you can visit the Italian G6PD Deficiency Association’s website at www.g6pd.org. They have published an in-depth list of medications to be avoided for those with a G6PD deficiency.
What Causes Glucose-6-Phosphate Dehydrogenase Deficiency?
The Gd gene is responsible for creating an enzyme known as G6PD. This gene resides on a part of the X chromosome, so it is inherited in a manner linked to this chromosome. A deficiency in G6PD can sometimes be caused by mutations, or changes, in the gene that alter the structure of the protein it creates. These changes can reduce the enzyme’s activity or the amount of enzyme that is produced.
Currently, we know of 186 different mutations in the human G6PD gene. Most of these mutations affect just a single part of the gene. However, it’s important to note that none of these mutations fully switch off the G6PD gene, because doing so would be fatal for a developing baby in the womb.
Risk Factors and Frequency for Glucose-6-Phosphate Dehydrogenase Deficiency
The enzyme defect known as G6PD is the most widespread of its kind, impacting over 400 million people globally. More men have this condition than women, which is primarily due to inheritance through the X chromosome. This enzyme deficiency is particularly common in tropical and subtropical regions.
Interestingly, studies show that people with G6PD deficiency seem to be less likely to get uncomplicated malaria; however, this doesn’t appear to be the case for severe types of malaria. Researchers are still investigating why this might be.
When it comes to ethnic groups, G6PD deficiency tends to be more prevalent among people of African, Mediterranean, or Asian descent. This might be because the enzyme defect could possibly provide some protection against malaria.
Signs and Symptoms of Glucose-6-Phosphate Dehydrogenase Deficiency
G6PD deficiency is a condition that doesn’t show symptoms in most patients throughout their lives. However, it can affect people differently based on their age. Newborns with G6PD deficiency are at a higher risk of developing severe jaundice, also known as neonatal hyperbilirubinemia. They are twice as likely to develop this condition compared to other newborns. In fact, around 20% of extreme jaundice cases, called kernicterus, are linked to G6PD deficiency. Symptoms of this severe condition include extreme sleepiness, poor muscle tone, and lethargy. Though it’s rare, G6PD deficiency should be suspected in any newborn who shows signs of jaundice within the first 24 hours of life, has a sibling who had neonatal jaundice, or has a bilirubin level that’s higher than the 95th percentile.
In adults, G6PD deficiency often presents symptoms similar to those of hemolytic anemia or those associated with the spleen trapping too many red blood cells, known as red blood cell sequestration. Some common symptoms of G6PD deficiency in adults are:
- Paleness
- Jaundice
- Fatigue
- Enlarged spleen
- Dark urine
Testing for Glucose-6-Phosphate Dehydrogenase Deficiency
When checking newborn babies for jaundice, doctors typically observe their skin under good lighting to see if it’s yellow. They might also do tests to measure levels of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB), substances that are usually present in higher quantities in babies with jaundice. A chart called an hour-specific bilirubin nomogram is used to assess the risk level in newborns with elevated bilirubin levels, which aids in deciding the best treatment.
Special tests for a condition called G6PD deficiency are available, but these aren’t commonly done in the US. Nonetheless, these tests should be considered in babies who have severe jaundice that doesn’t improve with light therapy or who have family history or background that might suggest G6PD deficiency. G6PD deficiency tests usually involve a quick fluorescent spot test to detect a specific reaction in the body. Another method is spectrophotometric analysis, which uses light to measure chemical concentrations.
For older patients experiencing complications related to G6PD deficiency, evaluation involves a thorough review of their medical and family history, including any new medications they might be taking. It’s also important to check for any possible infections, which could trigger a crisis in G6PD deficient patients where red blood cells break down faster than the body can handle (hemolysis). Lab tests may include a complete blood count, bilirubin levels, reticulocyte (young red blood cell) count, serum aminotransferases (liver enzymes), and lactate dehydrogenase (an enzyme that helps produce energy in the body). A test of blood cells under a microscope (peripheral blood smear) can show signs of hemolysis, like broken red blood cells (schistocytes) and damaged hemoglobin (Heinz bodies).
Treatment Options for Glucose-6-Phosphate Dehydrogenase Deficiency
In newborn babies, the treatment is mainly about dealing with jaundice and preventing a severe type of brain damage known as kernicterus. This often involves the use of light therapy, following widely accepted guidelines. If the condition is particularly serious, the baby may need to undergo a procedure known as an exchange transfusion.
In older patients, the plan of action depends a lot on how the patient is doing as a whole. If the condition is less severe, it may be managed by comforting and caring for the patient, stopping the use of any harmful substances, and avoiding any triggers that could make the situation worse. If there are signs of infection, then these will also be treated as appropriate. However, if the case is more severe, blood transfusions may be needed.
What else can Glucose-6-Phosphate Dehydrogenase Deficiency be?
G6PD deficiency might be confused with several other health conditions due to similar characteristics. The list of conditions to be considered for diagnosis include:
- Autoimmune hemolytic anemia – a condition where your own body destroys your red blood cells
- Disorders related to bilirubin conjugation like Gilbert syndrome – conditions affecting how your body processes bilirubin, a substance produced during the breakdown of red blood cells
- Hemolytic disease of the newborn – a condition causing a newborn baby’s red blood cells to breakdown
- Hereditary spherocytosis – a genetic disorder affecting red blood cells
- Sickle cell anemia – an inherited form of anemia
- Thalassemia – another type of inherited anemia
Remember, these conditions show similar symptoms and issues like G6PD deficiency. Therefore, differentiating between them is key to diagnosing a patient accurately.
