G6PD Deficiency is a genetic disorder found mostly in people of African, Asian, Middle Eastern and Mediterranean decent which can cause anemia under certain conditions. Although it can be fatal under the right circumstances, it is quite easy to control when you know how.
The proper name for it is Glucose 6 Phosphate Dehydrogenase Deficiency, which is why it has a short name. Back in the 1950′s and 1960′s we called it Familial Congenital Nonspherocytic Hemolytic Anemia Glucose 6 Phosphate Dehydrogenase Deficiency. And I had to memorize it so I could tell the doctor if I ever had to. This genetic disorder is basically an anomaly of the gene on the X-chromosome that controls the production of G6PD in cells.
G6PD is an enzyme which has the main roll of helping cells convert carbohydrates into a form they can use. In the process of doing that another enzyme is produced called reduced glutathione. This enzyme is a very powerful antioxidant. Since those with G6PDD don’t have enough G6PD, they don’t produce enough reduced glutathione to protect cells from oxidative stress. In all other cells except red blood cells (RBC) it isn’t critical as they have other means of protection. But for RBC’s it is a deadly matter.
When RBC’s are exposed to oxidative stress, the cell membrane either bursts or is damaged because there is no, or not enough reduced glutathione to protect them. So, what is this oxidative stress and how do I prevent it, you might ask. Good question. In fact, that is the most important question you could ask. If you can learn how to prevent oxidative stress, you can learn how to prevent RBC’s from dying from it, thus the main symptom of G6PDD is averted. The answer is not so simple, however.
There are quite a few things that cause oxidative stress and they are in three main categories. Infections. Some infectious diseases cause oxidative stress. Some viruses (flu, colds) and some germ infections can cause it. So learning how to prevent them is a very good idea. Keeping our immune systems healthy and doing other things to help prevent being exposed to these diseases is vital.
Drugs. There are many drugs that cause oxidative stress. We maintain a list of drugs to avoid on this website to help you make decisions about the medications you take. This list also contains some other substances that are very harmful. Some of them include naphthalene (moth balls), blue food color and menthol (artificial mint flavor).
Foods. This is the longest list as it contains all legumes (beans, peas, lentils). This list would be shorter if not for soy. Soy has made its way into our food supply in a big way. In fact it is hard to find prepared foods without it. So, we make our own foods from scratch a lot.
So where did I get it? As it turns out, African and Asian people have about ten to fifteen percent of their population affected by it, but the good news is that for the most part it is milder than the other main groups with it. It is also pretty common in Mediterranean (Italian, Greek, Sephardic Jews) and Middle Eastern populations. Some of them can have rates as high as sixty percent. To make matters worse, the Mediterranean variant is very severe. Oh, did I mention there are over four hundred different variants? This fact makes things a bit complicated. And it turns out that there is one other group that has it. You guessed it. My group.
Not as many of us have it, but the ones who do tend to be very severe. There are about eighty variants with something called Chronic Non-Spherocitic Hemolytic Anemia (CNSHA) associated with them. Don’t you love these million dollar names? Big name for a bad condition. Simply put, CNSHA means that we are always hemolyzing, whether we come into contact with triggers or not.
In 1956 a man named Dr. Beutler published a medical paper on his discovery. A few years prior to that, the Drug industry commissioned him and his group to find out why some people became anemic when given Primaquine (a drug used for Malaria). His team discovered that a very old disease called Favism caused it. He called it G6PDD. He used volunteer inmates in an Illinois prison to do his studies on, and my family is from Illinois. I don’t think any of them were in that prison, but somehow, we became involved in that research.
We lived in Montana at the time, but my mother got regular updates on what was going on and how it affected us from other members of our family. Which was a good thing, because in 1956 I had the first hemolytic crises that I can remember. Had my mother not known what to do, I would have died.
Up to this time we knew G6PDD by a much shorter name. The “family blood disease” and several of my family had died from it. This morning I got a call from a lady needing help…Continued on next page.
She told me about her family’s experience with G6PDD. Her father had died from G6PDD complications during an operation. Her son was diagnosed with G6PDD at two months of age. She didn’t know she had G6PDD until years later when she was almost 50 years old. All boys get G6PDD from their mother. Period. There is no other way for a boy to get it. If he got it from his mother, she also has it, but for women, G6PDD is a somewhat different matter. Here’s why.
Women have two X-chromosomes, while men only have one and G6PDD is controlled by a gene on the X-chromosome. When Dr. Beutler discovered G6PDD he and others thought that if one of the woman’s X-chromosomes was normal and one had G6PDD, the normal one would compensate for the one with G6PDD. They call that a recessive trait and they thought that women would not have symptoms (be asymptomatic, not react to triggers). They were wrong, but this notion was spread through the medical establishment for many years and still persists. Most people, including doctors, still believe that women are asymptomatic unless BOTH of their X-chromosomes are affected by G6PDD.
When a woman has only one affected X-chromosome, we say she is partially deficient. When both of them are affected, she is fully deficient. In either case, she can pass G6PDD on to her children. To read more about how G6PDD affects women, see the Women with G6PD Deficiency page. Because of this myth, my mother thought she was not affected by G6PDD. Had I known then, what I know now, I may have been able to help her and prolong her life.
Another problem with partially deficient women is that they almost always test negative for G6PDD using standard screening tests. I cannot count the number of women who have contacted me saying “no one in my family has G6PDD, so why does my baby have it? I don’t have it, I was tested and it came back negative.”
The only tests that can find G6PDD in partially deficient women are G6PD Quantitative tests. And since not all of a partially deficient woman’s children will get G6PDD and then the girls will be partially deficient, it can go for generations without anyone knowing. Then a boy gets it and everyone is surprised. See the G6PD Deficiency Inheritance page for more information.
This did not happen in my family. My mother is one of ten children and her mother is one of thirteen children. There was always at least one and usually more boys that had it and in my family ALL the boys know it when they have it. We spend a lot of time in the hospital getting blood, especially when young.
So, how do you keep from having symptoms (hemolysis)? Can you live a normal life when you have G6PDD? That is the topic for the next page.
After I reached upper teens, I pretty much forgot about G6PDD. But that was a serious mistake. We didn’t know as much back then as we do now, and I continued to follow Dr. Beutler’s recommendations. I was religious about staying away from everything on his avoid list. Some drugs, fava beans, methaline blue and moth balls. I always told my doctor that I had G6PDD, only I called it by the long name I had learned as a child. They all looked at me with a puzzled look on their face. No one knew what I was talking about. A few went to the trouble of analyzing the name to see what it might mean, but most just shrugged and said, “Never heard of it.”
As I got older, a few asked me if I had African ancestors. And as I got older, more of them would say they had heard of it in medical school, but not since. Progress has been painfully slow. Especially for a condition that affects 700 million people world wide and is touted as the most common enzyme deficiency in the world. And to make matters worse, medical schools were not teaching them the truth.
So I went from teens to forties without recognizing what was happening to me. My skin was a bit yellow all the time, my urine was always dark and I was a bit on the tired side most of the time, but I thought I was fine. Boy, was I wrong. In my forties I began having health problems. Tingling in my feet. Arthritis and joint pain that would appear and then go away. Nobody had the faintest idea what was wrong with me. I spent over $10,000.00 USD at the Mayo Clinic, among others, trying to find out what was wrong with me.
My feet got worse and the arthritis got worse. My eyes began bothering me. All the doctors said it had nothing to do with G6PDD, but every other test they did came up negative. I was pronounced healthy as a horse, but a horse that would be in pain for the rest of its life. They gave it a name. Peripheral Neuropathy (PN).
I became resigned to my fate and pretty much gave up. The pain in my legs and feet got so bad that I started looking for something to help. I found a study in San Francisco that was doing research on PN pain and they agreed to put me in the program. Basically, it was taking an Opium derived pain killer for a six month period.
The medicine had to be taken slowly at first and stopped slowly when the study was over, but I finally lived pain free for the first time in years. I was on cloud nine. Not high, as in a drugged state, but it just felt wonderful to be pain free. Then the other shoe dropped.
After taking the last pill, the pain came back worse than ever. I sat in the Doctor’s office a cried the pain was so bad. It took several months for my body to readjust to the pain and I was miserable. I learned a valuable lesson. Pain medicine will always quit working at some point and when it does, the pain will be much worse than before. After returning to my old way of living, (avoiding all medicine and doctors unless I was dying) my health continued to get worse. But in 2007 things changed. I discovered a G6PDD forum.
I became obsessed with learning how to fix my problems. The more I learned, the more I wanted to share this new knowledge with others. Learning about all the triggers was the biggest thing I had to learn and the hardest to accept. Grocery stores became very frustrating places to go. More times than not I would leave without buying anything. I was looking for the wrong things.
All my life I have gone to the grocery store and bought food based a lot on its convenience factor. Bread already made. Food already cooked and ready to eat. Just throw it in the microwave type foods. But, unfortunately, the prepared food manufacturers have increasingly added soy and other harmful things to their products, and soy is a big trigger. For a list of things to avoid, go to the Food to avoid and Drugs to Avoid pages. For this discussion, lets just say that I thought I would never be able to eat again.
Fortunately, that was entirely untrue. I just needed to make a few adjustments in what I bought. The first thing I had to come to grips with is the fact that prepared foods just were not going to work for me. I was going to have to learn to cook.
My mother was a wonderful cook, but she had passed away a few years earlier. The Food Network on TV became my new channel of choice and I spent hours every day watching it and learning. I figured that if I was going to have to learn to cook, I might as well be good at it. Besides, I missed my mother’s cooking anyway.
Another thing I learned is that diet was extremely important. It turns out that hemolysis has a price. Our body has to make more RBC’s and clean up the mess created by hemolysis. That takes resources and puts extra strain on our liver, spleen, heart, bone marrow, etc. and it takes the right foods to keep them going strong. So it was time to learn about nutrition.
What I have learned about nutrition is on the diet suggestions page. I cannot emphasize enough how much people with G6PDD need to eat right and stay healthy. If and when the time comes that we have a hemolytic crises, we will need all the strength our bodies can provide. Remember what I said about infections causing hemolysis? We need a healthy body to ward them off.
There are a few other general points I should make before I end this discussion. We’ll tackle them on the next page.
More men have it than women
This is not true, nor is it logical. Women can get it from either parent, while men only get it from mom. It just doesn’t make sense that more men would have it, but where this myth came from is the failure of most screening tests to detect women who have it. Also, because most women have less severe reactions to triggers, it was just assumed that they didn’t have it and were just carriers. A carrier is someone who passes something on to their children, but are not symptomatic themselves. We discussed that earlier.
In patients with acute hemolysis, testing for G6PD deficiency may be reported falsely negative because older RBC’s (erythrocytes) with less enzyme activity have been hemolyzed. Young erythrocytes and reticulocytes (new RBC’s) have normal or near-normal enzyme activity.
This will be a bit technical, but the terminology is necessary. Diagnosis is made by a quantitative spectrophotometric analysis or, more commonly, by a rapid fluorescent spot test detecting the generation of NADPH from NADP. The test is positive if the blood spot fails to fluoresce under ultraviolet light.
In field research, where quick screening of a large number of patients is needed, other tests have been used, however, they require confirmatory testing to confirm an abnormal result.
Tests based on polymerase chain reaction detect specific mutations and are used for population screening, family studies, or prenatal diagnosis.
An estimated 700 million people (10 percent of the population) world wide are G6PD Deficient. It is most common among people of Mediterranean, African, Asian and Middle Eastern decent though recent data produced by modern testing is not available. This website gets visits from almost every country on earth. The only countries not represented are very technologically challenged. New tests are much more accurate and suggest the number of G6PD Deficient people is higher than now reported, especially in women.
As an example, the Philippines, which showed few or no cases on G6PD Deficiency distribution maps, now that newborn screening has been implemented, is reporting that 12% of its population is affected.
More than 440 different variants of G6PD Deficiency have been identified so far ranging from severe to mild. More than 80 of them are accompanied by Chronic Non-spherocytic Hemolytic Anemia. G6PDD is commonly put into one of three classes as follows:
- Class I – Less than 10% G6PD activity accompanied by Chronic Non-spherocitic Hemolytic Anemia (CNSHA). The most severe form of G6PDD.
- Class II – Less than 10% G6PD activity. Severe.
- Class III – 10% – 60% G6PD activity. Moderate to mild.
There are two other classes that range from very mild to too much G6PD, but are not considered here as they do not pose much of a problem.
Favism has been known since antiquity. Everyone with Favism is G6PD Deficient. The term comes from the Fava Bean and those with Favism hemolyze when they come into contact with the bean. See the Favism Page for more information.
Treatment or cure
No. There is no known cure nor do you grow out of it. It is a life long condition. The only thing you can do is avoid substances which cause oxidative stress and that use G6PD. Carbohydrates require G6PD for the body to change them into energy for example. Legumes (especially the Fava Bean) contain the proteins vicine, convicine and isouramil which cause hemolysis. Not all legumes contain these ingredients, so there are other substances in them that are the triggers. We just don’t know what they are yet.
Symptoms include hemolytic anemia caused by ingestion or exposure to certain triggers. Anemia in turn causes jaundice, pale skin or finger nails, lethargy, exhaustion, shortness of breath and fever, among others. See the Signs of Severe Hemolysis page. These symptoms usually go away on their own when exposure to the trigger is removed.