Nearly half a billion people on the planet -- around one out of every fifteen individuals -- are afflicted with a condition that is largely unknown in the popular consciousness. While much time, angst, energy, and wealth is spent on diseases du jour such as the swine flu, there are precious few places to find solid information about one of the world's most common and widespread afflictions. Beyond simply being a matter of health care, this situation raises profound questions about social justice and global equity that deserve consideration in the public debate about how our medical resources are best utilized.
First, a few basics: the ailment is known as G6PD deficiency (for glucose-6-phosphate dehydrogenase) and, according to a 2008 article in The Lancet, it "is the most common human enzyme defect, being present in more than 400 million people worldwide." It's a genetic condition first isolated over 50 years ago wherein the body doesn't have enough of the enzyme G6PD, which helps red blood cells function normally. As described by an MD in a 2006 overview of the condition, "G6PD is one of many enzymes that help the body process carbohydrates and turn them into energy, and it also protects red blood cells from potentially harmful byproducts that can accumulate when a person ingests certain substances or when the body is fighting an infection." Basically, G6PD is an essential enzyme that is lacking in people with this widespread genetic disorder, and its absence leads to a condition that is closely related to other forms of anemia in which the body doesn't produce and maintain enough healthy red blood cells.
Some people with the condition appear (at least on the surface) asymptomatic. Others suffer acute anemic reactions (known as hemolysis) when they come into contact with triggering substances often found in foods, medicines, and hygiene products. These reactions generally cease when the trigger is eliminated, although over time the accumulation of these hemolytic episodes can lead to complications including chronic anemia, liver damage, and weakened heart functioning. Acute hemolytic reactions can sometimes necessitate blood transfusions, cause kidney failure, or (in rare cases) even result in death. G6PD-deficient individuals are also more prone to develop sepsis and similar complications following an injury. Newborns and babies are especially susceptible to such outcomes, making the ailment even more problematic because it remains largely undiagnosed and untreated, particularly in the United States.
And this leads directly to the another major aspect of the disorder, namely its telltale distribution pattern as to both geography and demographics. It is widespread throughout the Middle East, South Asia, the southern Mediterranean region, and Africa. It affects males more than females, with the latter functioning as carriers that are infrequently symptomatic. In particular, there's a strong racial divide of affliction in countries like the U.S., where "black males are most commonly affected, with a prevalence of approximately 10 percent," as noted in a 2005 article on diagnosing and managing the disease. Despite worldwide incidence and a disparate impact on African-American communities, this peer-reviewed article cogently observed that "newborn screening for G6PD deficiency is not performed routinely in the United States."
Indeed, the failure to screen for this pervasive ailment is at best negligent and at worst tinged with the broad brush of racism. In the United States, G6PD deficiency is found largely among people of color, and in particular African-American males, yet it is included in standard newborn "heel prick" tests only in Washington, D.C. and Pennsylvania. Black males in America already constitute a disadvantaged class across a wide range of socio-economic metrics, and this only exacerbates the situation. Moreover, when the rate of incidences of chronic anemia, hypertension, liver and kidney disease, and heart conditions among African-American males is considered, the failure to screen for G6PD deficiency among this population in particular suggests a pattern of reckless disregard for their health. More broadly, the politics of newborn screening are complex and bureaucratic, and are less based on medical necessity than expediency and cost. In the case of G6PD deficiency and other genetic conditions, the U.S. Department of Health and Human Services (HHS) impaneled an advisory committee on "Heritable Disorders in Newborns and Children," and in June 2004 the committee noted that only D.C. screened for the disorder and that "data is still being reviewed" on G6PD. By September 2004, the committee's discussion about G6PD mostly devolved upon "cost-effectiveness" and the "overwhelming lack of data" on the disorder in the U.S., with one member bluntly concluding: "We just don't have any data in this population, in the U.S., to say anything about G6PD." Another member addressed the cost-versus-health issue directly:
"I know if I were a parent of a child with G6PD ... I would hope that we'd be looking at more than just the cost-effectiveness. It may not be cost-effective anywhere in the numbers, but it certainly would be cost-effective to saving that child."
The committee chair, an MD, concurred:
"I think one of the things that is probably not in any of the cost-benefit analyses are the direct costs to the families that are incurred when they have a child with a condition that is missed. I think all of us who have been in this field are aware of families that have had extraordinarily expensive odysseys. They fundamentally end up picking up the tab for this through time off from work, travel, confusion, the whole nine yards, and so forth."
Following the 2004 hearings, the March of Dimes noted that in January 2005 the American College of Medical Genetics dropped G6PD deficiency from its recommended newborn screening protocol, effectively leaving it in a state of limbo and thus perpetuating the ignorance and lack of medical knowledge that we still see today. As Jill Fisch (Save Babies Through Screening Foundation) opined before the HHS committee, the challenges faced by people seeking accurate information are significant:
"I have had many cases brought to my attention where a family has prepared to have their child supplementally screened, and have been talked out of it while still at the hospital. These families then had to seek the screening through their pediatricians. It would be quite tragic if a child suffered from a disorder and had serious complications while the family was trying to get the child screened. One pediatrician told a mother, it is too time consuming to perform the tests. Perhaps most disturbing was the call I received from a New York family. The mother had G6PD and wanted to have her baby screened. The pediatrician refused to perform the testing, and called it a marketing ploy. I had to make arrangements for the mother to have the screening performed. I also had to help her find a new pediatrician. There needs to be an educational program in place for the medical community so that they become informed, and this does not happen."
The lack of adequate screening and medical data leads to some disconcerting implications due to the fact that the primary mode of treatment for the disorder is basic lifestyle management -- meaning that if screening was more widespread, those afflicted could be taking immediate and effective measures to curtail the disease's negative impacts. Essentially, when triggering substances are eliminated, hemolysis ceases and both acute and long-range implications are abated. (Interestingly, fava beans are widely known as a major trigger substance, leading to the oft-used colloquial name of favism for the disorder and the intriguing historical speculation that "favism has been known to exist since antiquity; the Greek philosopher and mathematician Pythagoras was said to have warned his disciples against the dangers of eating fava beans.") Since the vast majority of G6PD-deficiency cases in the U.S. are undiagnosed, however, people continue to unknowingly ingest triggers and in some cases wind up with chronic and even life-threatening conditions as a result. Better screening, diagnosis, and public information could improve not only peoples' health but also help to contain rising health care costs in the process.
And yet, despite increased scientific interest in the subject in recent years, there's almost no coordinated effort to inform people about this widespread disease. It's very difficult to locate accurate information about trigger substances, and no official clearinghouse exists to bring together the best practices and information about treating the disease. Food products and medicines are not labeled in a manner that could help G6PD sufferers make informed choices, and many doctors are likewise left to play a guessing game when it comes to advising their patients. A number of common food-borne infectious agents (such as salmonella and E-coli) are also potential hemolysis triggers, as are certain strains of ailments such as streptococcus and influenza, suggesting that better public health and hygiene practices could ameliorate the disorder's effects. Overall, if a concerted initiative based on screening, research, and information dissemination was undertaken, the benefits would be immediate and substantial both in the U.S. and around the world.
But as things currently stand, it's nearly impossible for a person with G6PD to know with assurance how to manage the condition. The food supply (plus personal health care and cleaning products as well) in the U.S. in particular is so heavily-laden with preservatives and chemical agents that one almost has to be a trained scientist to deconstruct labels these days. Many products aren't even accurately labeled in the first instance, and there's little oversight of additives that are found in a wide array of products. For G6PD sufferers, among the critical substances that are frequently contraindicated are legumes, sulfites, analgesics, and other strong blood oxidants such as blueberries and henna, to name just a few. Items such as soy -- an immensely widespread additive that often triggers hemolysis in G6PD sufferers -- are hidden in many products and are thus ingested by people despite their best attempts to avoid it, since even when it isn't expressly mentioned on a label it can be part of any of the additives, binders, and preservatives (the same is true for sulfites and other oxidants). Consider the implications of this when you see pervasive items such as "natural flavors," "monosodium glutamate," or "artificial coloring" in a given food product: any of these can and likely do contain G6PD triggers, among other potentially harmful ingredients. Moreover, beyond simply documenting and avoiding trigger substances, almost no research currently exists on potentially beneficial food items that could have a therapeutic and prophylactic effect on people with G6PD deficiency and related anemic disorders.
Official neglect notwithstanding, there are some fine resources beginning to appear, but they are uncoordinated and often difficult to interpret. Genetics Home Reference has some useful links, and Wikipedia has a very scientific and well-documented explanation. A much more user-friendly and thorough website is G6PDDeficiency.org, which has lists of dietary suggestions, trigger substances, and recent articles among its many resources, and also provides a G6PD forum and discussion listserv. Perhaps the most useful site currently available is the G6PD Deficiency Association, which "offers assistance to persons affected by the G6PD enzyme deficiency and their families, including helping them protect their social rights and collect their benefits, informing and educating affected persons and the medical community on all aspects of the deficiency." The site -- initiated in 1996 with support from Dr. Ernest Beutler, who first identified the disorder in the 1950s -- contains comprehensive lists of items to avoid and drugs that are safe, links to important research articles, an active discussion forum, and vital neonatal insights that are otherwise difficult to find. Still, these nascent resources are informal and somewhat anecdotal at this point (although the information is well-researched), leaving people with the disorder in the unenviable position of having to resort to mere educated guesses about their health.
Quite likely the single biggest piece of good news about G6PD deficiency is that it is widely understood to confer protection against malaria, in particular the most deadly form of that disease. Although the precise medical reason for this conferral of immunity remains to be fully understood, when the distribution pattern of the disease is overlain with areas prone to malarial infections, the correlation becomes evident. While it has even been observed that the presence of G6PD deficiency could provide "an evolutionary advantage" in malarial endemic environments, it of course remains the case that one must first survive and surmount the ailment itself (and its attendant complications) in order to realize any of its ancillary immunological benefits.
Unsurprisingly, these implications have drawn the interest of the U.S. military. A 2004 study of 526 military personnel confirmed the disorder's clear racial divide, and found incidence rates resembling that of the general U.S. population. Among those tested in the study, black females had a 12.9% rate of G6PD deficiency, black males registered at 11.5%, white females had a 0% rate, and white males came in at 0.3%. That same year, the U.S. Army issued a document from its Medical Command announcing a G6PD deficiency screening program, after determining that certain anti-malarial agents being issued to soldiers could cause "potentially life-threatening hemolysis" in afflicted individuals. Nonetheless, despite its awareness of the disorder, the Army's treatment regimen for G6PD-deficient soldiers was merely the issuance of "alert tags" warning that the anti-malarial drug primaquine should not be administered and that similar hemolysis-triggering drugs should be administered with caution. No mention was made of food-related hemolysis triggers, lifestyle therapies, or other sources of useful information.
In the end, there remains a great need for more education and coordination regarding this prevalent condition that affects hundreds of millions of individuals. While there is no known cure at present for genetic conditions such as G6PD deficiency, gene therapy may hold some promise in the future. More to the point is that people with the condition simply need to avoid known trigger substances and oxidative stressors, which is actually good advice for anyone concerned about food additives and the overuse of pharmaceuticals. Indeed, becoming more informed about our patterns of consumption and the viable alternatives to mass-produced food and health products is an important component of G6PD self-care in particular and of leading a healthier, more conscious lifestyle in general. In this sense, it may be possible to turn a condition based on an ostensible "deficiency" into something that helps to promote an abundance of knowledge and resources for us all.
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