G6PDH deficiency
   HOME

TheInfoList



OR:

Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to
red blood cell breakdown Hemolysis or haemolysis (), also known by several other names, is the rupturing ( lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo ...
. Most of the time, those who are affected have no symptoms. Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. Complications can include anemia and
newborn jaundice Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral pal ...
. Some people never have symptoms. It is an X-linked recessive disorder that results in defective glucose-6-phosphate dehydrogenase enzyme. Glucose-6-phosphate dehydrogenase is an enzyme which protects red blood cells, which carry oxygen from the lungs to tissues throughout the body. A defect of the enzyme results in the premature breakdown of red blood cells. This destruction of red blood cells is called hemolysis. Red blood cell breakdown may be triggered by infections, certain medication, stress, or foods such as fava beans. Depending on the specific mutation the severity of the condition may vary. Diagnosis is based on symptoms and supported by blood tests and
genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
. Affected persons must avoid dietary triggers, notably fava beans. This can be difficult, as fava beans may be called "broad beans" and are used in many foods, whole or as flour. Falafel is probably the best known, but fava beans are also often used as filler in meatballs and other foods. Since G6PD deficiency is not an allergy, food regulations in most countries do not require that fava beans be highlighted as an allergen on the label. Treatment of acute episodes may include medications for infection, stopping the offending medication, or blood transfusions. Jaundice in newborns may be treated with
bili light A bili light is a light therapy tool to treat newborn jaundice (hyperbilirubinemia). High levels of bilirubin can cause brain damage (kernicterus), leading to cerebral palsy, auditory neuropathy, gaze abnormalities and dental enamel hypoplasia. T ...
s. It is recommended that people be tested for G6PDD before certain medications, such as primaquine, are taken. About 400 million people have the condition globally. It is particularly common in certain parts of Africa, Asia, the Mediterranean, and the Middle East. Males are affected more often than females. In 2015 it is believed to have resulted in 33,000 deaths.


Signs and symptoms

Most individuals with G6PD deficiency are
asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
. Most people who develop symptoms are male, due to the X-linked pattern of inheritance, but female carriers can be affected due to unfavorable lyonization or skewed X-inactivation, where random inactivation of an X-chromosome in certain cells creates a population of G6PD-deficient red blood cells coexisting with unaffected red blood cells. A female with one affected X chromosome will show the deficiency in approximately half of her red blood cells. However, in some cases, including double X-deficiency, the ratio can be much more than half, making the individual almost as sensitive as males. Red blood cell breakdown (also known as hemolysis) in G6PD deficiency can manifest in a number of ways, including the following: * Prolonged neonatal jaundice, possibly leading to kernicterus (arguably the most serious complication of G6PD deficiency) * Hemolytic crises in response to: ** Illness (especially infections) ** Certain
drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...
(see below) ** Certain foods, most notably broad beans, from which the word ''favism'' derives ** Certain chemicals ** Diabetic ketoacidosis * Hemoglobinuria (red or brown urine) * Very severe crisis can cause acute kidney injury Favism is a hemolytic response to the consumption of fava beans, also known as broad beans. Though all individuals with favism show G6PD deficiency, not all individuals with G6PD deficiency show favism. The condition is known to be more prevalent in infants and children, and G6PD genetic variant can influence chemical sensitivity. Other than this, the specifics of the chemical relationship between favism and G6PD are not well understood.


Cause

G6PD deficiency results from mutations in the G6PD gene. G6PD gene contributes to the production of glucose-6-phosphate dehydrogenase. Chemical reactions involving glucose-6-phosphate dehydrogenase produce compounds that prevent reactive oxygen species from building up to toxic levels within red blood cells. If reduction in the amount of glucose-6-phosphate dehydrogenase or alteration of structure occurs due to the mutations of G6PD gene, the enzyme loses it protective role and leads to the accumulation of reactive oxygen species and thus damage of red blood cells.


Triggers

Carriers of the underlying mutation do not show any symptoms unless their red blood cells are exposed to certain triggers, which can be of four main types: * Foods (fava beans is the hallmark trigger for G6PD mutation carriers), * Certain medicines including aspirin, quinine and other
antimalarials Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
derived from quinine. *
Moth balls Mothballs are small balls of chemical pesticide and deodorant, sometimes used when storing clothing and other materials susceptible to damage from mold or moth larvae (especially clothes moths like ''Tineola bisselliella''). Composition Older ...
(
naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08  ppm by mass. As an aromati ...
) * Stress from a bacterial or viral infection.


Drugs

Many substances are potentially harmful to people with G6PD deficiency. Variation in response to these substances makes individual predictions difficult. Antimalarial drugs that can cause acute hemolysis in people with G6PD deficiency include primaquine,
pamaquine Pamaquine is an 8-aminoquinoline drug formerly used for the treatment of malaria. It is closely related to primaquine. Synonyms *Plasmochin *Plasmoquine *Plasmaquine Uses Pamaquine is effective against the hypnozoites of the relapsing malarias ...
, chloroquine, and hydroxychloroquine. There is evidence that other antimalarials may also exacerbate G6PD deficiency, but only at higher doses.
Sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
(such as
sulfanilamide Sulfanilamide (also spelled sulphanilamide) is a sulfonamide antibacterial drug. Chemically, it is an organic compound consisting of an aniline derivatized with a sulfonamide group. Powdered sulfanilamide was used by the Allies in World War II ...
,
sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Listeria monocytogenes' ...
, and
mafenide Mafenide (INN; usually as mafenide acetate, trade name Sulfamylon) is a sulfonamide-type medication used as an antibiotic. It was approved by the FDA in 1948. Uses Mafenide is used to treat severe burns. It is used topically as an adjunctive t ...
), thiazolesulfone,
methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
, and
naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08  ppm by mass. As an aromati ...
should also be avoided by people with G6PD deficiency as they antagonize folate synthesis, as should certain
analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s (such as phenazopyridine and acetanilide) and a few non-sulfa antibiotics ( nalidixic acid,
nitrofurantoin Nitrofurantoin is an antibacterial medication used to treat urinary tract infections, but it is not as effective for kidney infections. It is taken by mouth. Common side effects include nausea, loss of appetite, diarrhea, and headaches. Rarely ...
, isoniazid,
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...
, and
furazolidone Furazolidone is a nitrofuran antibacterial agent and monoamine oxidase inhibitor (MAOI). It is marketed by Roberts Laboratories under the brand name Furoxone and by GlaxoSmithKline as Dependal-M. Medical uses Furazolidone has been used in human ...
).
Henna Henna is a dye prepared from the plant ''Lawsonia inermis'', also known as the henna tree, the mignonette tree, and the Egyptian privet, the sole species of the genus ''Lawsonia''. ''Henna'' can also refer to the temporary body art resulting fr ...
has been known to cause hemolytic crisis in G6PD-deficient infants. Rasburicase is also contraindicated in G6PD deficiency. High dose
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
vitamin C has also been known to cause haemolysis in G6PD deficiency carriers; therefore, G6PD deficiency testing is routine before infusion of doses of 25 g or more.


Genetics

Two variants (G6PD A− and G6PD Mediterranean) are the most common in human populations. G6PD A− has an occurrence of 10% of Africans and African-Americans while G6PD Mediterranean is prevalent in the Middle East. The known distribution of the mutated allele is largely limited to people of Mediterranean origins (Spaniards, Italians, Greeks, Armenians, Sephardi Jews and other Semitic peoples). Both variants are believed to stem from a strongly protective effect against ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'' and '' Plasmodium vivax'' malaria. It is particularly frequent in the Kurdish Jewish population, wherein approximately 1 in 2 males have the condition and the same rate of females are carriers. It is also common in African American, Saudi Arabian, Sardinian males, some African populations, and Asian groups.''Glucose-6-Phosphate Dehydogenase Deficiency (G6PD)'' on The Jewish Genetic Disease Consortium (JGDC) websit

All mutations that cause G6PD deficiency are found on the long arm of the X chromosome, on band Xq28. The G6PD gene spans some 18.5 kilobases. The following variants and mutations are well-known and described:


Pathophysiology

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (see image, also known as the HMP shunt pathway). G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of this metabolic pathway that supplies reducing energy to cells by maintaining the level of the reduced form of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH maintains the supply of reduced glutathione in the cells that is used to mop up free radicals that cause
oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
damage. The pathway also stimulates catalase, an antioxidant enzyme. The G6PD / NADPH pathway is the ''only'' source of reduced glutathione in red blood cells ( erythrocytes). The role of red cells as oxygen carriers puts them at substantial risk of damage from oxidizing free radicals except for the protective effect of G6PD/NADPH/glutathione. People with G6PD deficiency are therefore at risk of hemolytic anemia in states of oxidative stress. Oxidative stress can result from infection and from chemical exposure to medication and certain foods. Broad beans, e.g., fava beans, contain high levels of
vicine Vicine is an alkaloid glycoside found mainly in fava beans, which are also called broad beans (''Vicia faba)''. Vicine is toxic in individuals who have a hereditary loss of the enzyme glucose-6-phosphate dehydrogenase. It causes haemolytic anaemi ...
,
divicine Divicine (2,6-diamino-4,5-dihydroxypyrimidine) is an oxidant and a base with alkaloidal properties found in fava beans and ''Lathyrus sativus''. It is an aglycone of vicine. A common derivative is the diacetate form (2,6-diamino-1,6-dihydro-4,5-p ...
, convicine and isouramil, all of which create oxidants. When all remaining reduced glutathione is consumed, enzymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to cross-bonding and protein deposition in the red
cell membranes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
. Damaged red cells are phagocytosed and sequestered (taken out of circulation) in the spleen. The hemoglobin is metabolized to
bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...
(causing
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
at high concentrations). The red cells rarely disintegrate in the circulation, so hemoglobin is rarely excreted directly by the kidney, but this can occur in severe cases, causing acute kidney injury. Deficiency of G6PD in the alternative pathway causes the buildup of glucose and thus there is an increase of advanced glycation endproducts (AGE). The deficiency also reduces the amount of NADPH, which is required for the formation of nitric oxide (NO). The high prevalence of
diabetes mellitus type 2 Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
and
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
in Afro-Caribbeans in the West could be directly related to the incidence of G6PD deficiency in those populations. Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome – see '' lyonization''), homozygous females have been described; in these females there is co-incidence of a rare
immune disorder An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...
termed chronic granulomatous disease (CGD).


Diagnosis

The diagnosis is generally suspected when patients from certain ethnic groups (see epidemiology) develop anemia,
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
and symptoms of hemolysis after challenges from any of the above causes, especially when there is a positive family history. Generally, tests will include: * Complete blood count and reticulocyte count; in active G6PD deficiency,
Heinz bodies Heinz bodies (also referred to as "Heinz-Ehrlich bodies") are inclusions within red blood cells composed of denatured hemoglobin. They are not visible with routine blood staining techniques, but can be seen with supravital staining. The presence o ...
can be seen in red blood cells on a blood film; * Liver enzymes (to exclude other causes of
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
); * Lactate dehydrogenase (elevated in hemolysis and a marker of hemolytic severity) * Haptoglobin (decreased in hemolysis); * A "
direct antiglobulin test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood ce ...
" (Coombs' test) – this should be negative, as hemolysis in G6PD is not immune-mediated; When there are sufficient grounds to suspect G6PD, a direct test for G6PD is the "
Beutler fluorescent spot test The Beutler test, also known as the fluorescent spot test, is a screening test used to identify enzyme defects.Beutler E, Mitchell M. New rapid for the estimation of red cell galactose-1-phosphate uridyl transferase activity. J Lab Clin Med 1968;7 ...
", which has largely replaced an older test (the Motulsky dye-decolouration test). Other possibilities are direct DNA testing and/or sequencing of the G6PD gene. The ''Beutler fluorescent spot test'' is a rapid and inexpensive test that visually identifies
NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
produced by G6PD under ultraviolet light. When the blood spot does not fluoresce, the test is positive; it can be falsely negative in patients who are actively hemolysing. It can therefore only be done 2–3 weeks after a hemolytic episode. When a macrophage in the spleen identifies a RBC with a Heinz body, it removes the precipitate and a small piece of the membrane, leading to characteristic "
bite cells A degmacyte or bite cell is an Poikilocytosis, abnormally shaped mature red blood cell with one or more semicircular portions removed from the cell margin, known as "bites". These "bites" result from the mechanical removal of denatured hemoglobin d ...
". However, if a large number of Heinz bodies are produced, as in the case of G6PD deficiency, some Heinz bodies will nonetheless be visible when viewing RBCs that have been stained with crystal violet. This easy and inexpensive test can lead to an initial presumption of G6PD deficiency, which can be confirmed with the other tests. Testing during and for many weeks after a haemolytic episode will lead to false negative results as the G6PD deficient RBC will have been excreted and the young RBC (reticulocytes)will not yet be G6PD deficient. False negative results will also be likely following any blood transfusions. For this reason, many hospitals wait for 3 months after a haemolytic episode before testing for G6PD deficiency. Females should have their G6PD activity measured by quantitative assay to avoid being misclassified by screening tests.


Classification

The World Health Organization classifies G6PD genetic variants into five classes, the first three of which are deficiency states. * Class I: Severe deficiency (<10% activity) with chronic (nonspherocytic) hemolytic anemia * Class II: Severe deficiency (<10% activity), with intermittent hemolysis * Class III: Moderate deficiency (10-60% activity), hemolysis with stressors only * Class IV: Non-deficient variant, no clinical sequelae * Class V: Increased enzyme activity, no clinical sequelae


Differential diagnosis

6-phosphogluconate dehydrogenase (6PGD) deficiency has similar symptoms and is often mistaken for G6PD deficiency, as the affected enzyme is within the same pathway, however these diseases are not linked and can be found within the same person.


Treatment

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks. In the acute phase of hemolysis, blood transfusions might be necessary, or even
dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation. Those affected should avoid drugs such as aspirin. Some patients may benefit from removal of the spleen ( splenectomy), as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency.


Prognosis

G6PD-deficient individuals do not appear to acquire any illnesses more frequently than other people, and may have less risk than other people for acquiring
ischemic heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
and cerebrovascular disease. However, a recent study revealed that G6PD deficiency increases the cardiovascular risk up to 70%. The risk conferred by G6PD deficiency is moderate compared with the impact of primary cardiovascular risk factors. Besides, a published review hypothesized that G6PD deficiency could reduce the antiplatelet efficacy of clopidogrel (clopidogrel resistance).


Epidemiology

G6PD deficiency is the second most common human enzyme defect after ALDH2 deficiency, being present in more than 400 million people worldwide. G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990. The
Mediterranean Basin In biogeography, the Mediterranean Basin (; also known as the Mediterranean Region or sometimes Mediterranea) is the region of lands around the Mediterranean Sea that have mostly a Mediterranean climate, with mild to cool, rainy winters and w ...
is where favism is most common, especially among Mizrahi Jews, Sardinians,
Cypriots Cypriots or Cypriot people may refer to: * The inhabitants of Cyprus ** Demographics of Cyprus * Cypriot people, or of Cypriot descent; this includes: **Armenian Cypriots **Greek Cypriots **Maronite Cypriots **Turkish Cypriots See also * Cypriot ...
, Greeks,
Egyptians Egyptians ( arz, المَصرِيُون, translit=al-Maṣriyyūn, ; arz, المَصرِيِين, translit=al-Maṣriyyīn, ; cop, ⲣⲉⲙⲛ̀ⲭⲏⲙⲓ, remenkhēmi) are an ethnic group native to the Nile, Nile Valley in Egypt. Egyptian ...
, and some African populations, including those who have these ancestries. Favism has also been documented outside of the Mediterranean basin, in other Middle Eastern and East Asian nations like Iraq, Iran, Bulgaria and China. Sardinia has the highest reported frequency of favism, with five instances per every 1,000 people. A side effect of this disease is that it confers protection against malaria, in particular the form of malaria caused by ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'', the most deadly form of malaria. A similar relationship exists between malaria and
sickle-cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
. One theory to explain this is that cells infected with the ''Plasmodium'' parasite are cleared more rapidly by the spleen. This phenomenon might give G6PD deficiency carriers an evolutionary advantage by increasing their fitness in malarial endemic environments. In vitro studies have shown that the ''Plasmodium falciparum'' is very sensitive to oxidative damage. This is the basis for another theory, that is that the genetic defect confers resistance due to the fact that the G6PD-deficient host has a higher level of oxidative agents that, while generally tolerable by the host, are deadly to the parasite.


History

The modern understanding of the condition began with the analysis of patients who exhibited sensitivity to primaquine. The discovery of G6PD deficiency relied heavily upon the testing of prisoner volunteers at
Illinois State Penitentiary Stateville Correctional Center (SCC) is a maximum security state prison for men in Crest Hill, Illinois, United States, near Chicago. It is a part of the Illinois Department of Corrections. History Opened in 1925, Stateville was built to ac ...
, a type of study which today is considered unethical and cannot be performed. When some prisoners were given the drug primaquine, some developed hemolytic anemia but others did not. In spite of these results, the US military administered the drug widely during the Korean War to prevent the relapsing infection caused by '' Plasmodium vivax'' hypnozoites. Numerous cases of hemolytic anemia were observed in US soldiers of North African and Mediterranean descent. After studying the mechanism through Cr51 testing, it was conclusively shown that the hemolytic effect of primaquine was due to an intrinsic defect of erythrocytes.


Society and culture

In both legend and mythology, favism has been known since antiquity. The priests of various Greco-Roman era cults were forbidden to eat or even mention beans, and Pythagoras had a strict rule that to join the society of the Pythagoreans one had to swear off beans. This ban was supposedly because beans resembled male genitalia, but it is possible that this was because of a belief that beans and humans were created from the same material.


References


External links


Family Practice Notebook/G6PD Deficiency (Favism)
{{DEFAULTSORT:Glucose-6-Phosphate Dehydrogenase Deficiency Hereditary hemolytic anemias Inborn errors of carbohydrate metabolism Wikipedia medicine articles ready to translate