Symptoms usually appear 24-48 hours after ingestion of fava beans and are related to the development of hemolytic anemia. Most prominent symptoms include weakness, headaches, pallor, abdominal pain, dark urine due to hemoglobinuria and in some cases jaundice [13]. Syncope was also documented in some cases [14], while kidney and liver function may be significantly impaired due to extensive hemolysis. Patients may report a history of these symptoms having already occurred, indicating previous fava bean ingestion. On physical examination, splenomegaly and jaundice may be observed.

• Splenomegaly

  Abdominal ultrasound may be used to detect gallstones and/or splenomegaly. Coombs' test is negative. [patient.info]

  He did not have hepatomegaly or splenomegaly. Laboratory workup revealed hemoglobin of 8 g/dL (14 g/dL at baseline), leukocytosis, hyperbilirubinemia, hemoglobinuria, elevated LDH, high reticulocyte index and low haptoglobin. [shmabstracts.com]

  On physical examination, splenomegaly and jaundice may be observed. [symptoma.com]

  Jaundice and splenomegaly are features of the extracellular contribution of red cell destruction. “Once a diagnosis of favism has been made, management is usually not difficult,” the authors assure us. [hematology.org]

  […] a partial deficiency that will not be detected reliably with screening tests. 7, 11, 12 G6PD deficiency is one of a group of congenital hemolytic anemias, and its diagnosis should be considered in children with a family history of jaundice, anemia, splenomegaly [aafp.org]

• Anemia

  Favism: A condition characterized by hemolytic anemia (breakup of red blood cells) after eating fava beans (Vicia fava) or being exposed to the pollen of the fava plant. [rxlist.com]

  anemias, not elsewhere classified D53.2 Scorbutic anemia D53.8 Other specified nutritional anemias D53.9 Nutritional anemia, unspecified D55 Anemia due to enzyme disorders D55.0 Anemia due to glucose-6-phosphate dehydrogenase [G6PD] deficiency D55.1 [icd10data.com]

  […] vizəm] Etymology: It, fava, bean an acute hemolytic anemia caused by ingestion of the beans or inhalation of the pollen from the Vicia faba (fava) plant. [medical-dictionary.thefreedictionary.com]

  Symptoms usually appear 24-48 hours after ingestion of fava beans and are related to the development of hemolytic anemia. [symptoma.com]

  […] fav·ism | \ ˈfä-ˌvi-zəm \ : a condition especially of males of Mediterranean descent that is marked by the development of hemolytic anemia upon consumption of fava beans or inhalation of fava bean pollen and is caused by a usually inherited deficiency [merriam-webster.com]

• Fever

  […] fa·vism ( fā'vizm ), An acute condition suffered after ingestion of certain species of beans, for example, Vicia faba, or inhalation of the pollen of its flower; characterized by fever, headache, abdominal pain, severe anemia, prostration, and coma; it [medical-dictionary.thefreedictionary.com]

  During a routine screening for G6PD deficiency in the Province of Matera (Southern Italy), an eleven-year-old boy was brought to our attention who had fever obviously caused by a viral infection, but who also had hepatosplenomegaly and haemoglobinuria [ncbi.nlm.nih.gov]

  These patients were mostly referred with urine discoloration and icterus, but there were other symptoms such as vomiting, fever, or abdominal pain. [onlinelibrary.wiley.com]

  They include headaches, dizziness, nausea, yawning --> vomiting, abdominal pain, and fever --> at this point, symptoms either spontaneously subside, or --> acute hemolytic anemia occurs. [poisonousplants.ansci.cornell.edu]

  Attack can cause the patient to feel headache, dizziness, fever, vomiting and diarrhea. The person can also feel abdominal pain. He may also feel tiredness all the time. [trivology.com]

• Weakness

  In the Favism patients, the Hp2-1 and Hp2-2 patterns exhibited the normal and weak (Hypo) type, whereas the G6PD deficient and normal samples did not show such a differentiation. [ncbi.nlm.nih.gov]

  Most prominent symptoms include weakness, headaches, pallor, abdominal pain, dark urine due to hemoglobinuria and in some cases jaundice. [symptoma.com]

  During a hemolytic crisis when a person's red cells rupture, the sufferer can have symptoms such as jaundice (yellow eyes and skin), paleness, weakness, fatigue, shortness of breath, chest pain, or fainting. [lydiakang.blogspot.com]

  Becker's muscular dystrophy, a milder form of Duchenne, which causes slowly progressive muscle weakness of the legs and pelvis. X-linked ichthyosis, a form of ichthyosis caused by a hereditary deficiency of the steroid sulfatase (STS) enzyme. [en.wikipedia.org]

• Pallor

  The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. [ncbi.nlm.nih.gov]

  Acute pallor due to anaemia. Haemoglobinuria causing the passage of dark or orangey-yellow urine. Jaundice. Patients with G6PD deficiency are prone to gallstones and splenomegaly due to recurrent, often subclinical, episodes of haemolysis. [patient.info]

  Examination revealed scleral icterus, conjunctival pallor and sublingual cyanosis. His arterial oxygen saturation (SaO2) was 86% on pulse-oximetry but 100% on arterial blood gas (ABG). [shmabstracts.com]

  Most prominent symptoms include weakness, headaches, pallor, abdominal pain, dark urine due to hemoglobinuria and in some cases jaundice. [symptoma.com]

  They may have: pale skin (pallor) persistent and/or severe tiredness dark coloured urine (wee) jaundice (yellow skin or eyes). [rch.org.au]

• Fatigue

  During a hemolytic crisis when a person's red cells rupture, the sufferer can have symptoms such as jaundice (yellow eyes and skin), paleness, weakness, fatigue, shortness of breath, chest pain, or fainting. [lydiakang.blogspot.com]

  Fabry disease ; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement. [en.wikipedia.org]

  Photo of Vicia fava Symptoms of favism Normally favism manifests as fatigue, fever or headache. Sometimes they manifest as vomiting, intestinal discomfort or dizziness which usually disappear within a week. [botanical-online.com]

  A well-described case history brings a topic alive as the authors describe the typical scenario of a boy aged two to 10 years, with acute fatigue, pallor, and abdominal pain. [hematology.org]

• Dyspnea

  Dyspnea, Orthopnea, and Paroxysmal Nocturnal Dyspnea. Butterworth Publishers. Archived from the original on 27 April 2018. Retrieved 15 August 2014. [en.wikipedia.org]

  Case Presentation: A 43 year old Albanian man without any significant past medical history, presented to the hospital with sudden onset intermittent dyspnea, chills and dark urine of 4 days duration. [shmabstracts.com]

  Sensitive individuals suffer from acute hemolytic anemia upon exposure with characteristic symptoms that include pallor, fatigue, dyspnea, nausea, abdominal and/or back pain, fever, and chills. [farrp.unl.edu]

• Sputum

  People with chronic obstructive pulmonary disease (COPD), most commonly emphysema or chronic bronchitis, frequently have chronic shortness of breath and a chronic productive cough. [2] An acute exacerbation presents with increased shortness of breath and sputum [en.wikipedia.org]

• Respiratory Distress

  Shortness of breath Other names Dyspnea, dyspnoea, shortness of breath (SOB), breathlessness, difficulty of breathing, respiratory distress Specialty Pulmonology Shortness of breath, also known as dyspnea, is the feeling that one cannot breathe well enough [en.wikipedia.org]

• Diarrhea

  Consumption of lectins can cause symptoms like vomiting, nausea and diarrhea. [foodsafetynews.com]

  Symptoms include dizziness, headache, vomiting, fever, jaundice, eosinophilia, and often diarrhea. The condition occurs primarily in persons of southern Italian extraction and is treated by blood transfusion and avoidance of fava beans and pollen. [medical-dictionary.thefreedictionary.com]

  Página 54 - Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. ‎ Página 51 - Selective IgA deficiency: presentation of 30 cases and a review of the literature. ‎ [books.google.es]

  Attack can cause the patient to feel headache, dizziness, fever, vomiting and diarrhea. The person can also feel abdominal pain. He may also feel tiredness all the time. [trivology.com]

  Nausea, abdominal pain and diarrhea may develop. Vomiting only occurs rarely. Within 6 to 24 hours, urine may become noticeably dark and can appear red, brown or even black. [rarediseases.org]

• Nausea

  Consumption of lectins can cause symptoms like vomiting, nausea and diarrhea. [foodsafetynews.com]

  They include headaches, dizziness, nausea, yawning --> vomiting, abdominal pain, and fever --> at this point, symptoms either spontaneously subside, or --> acute hemolytic anemia occurs. [poisonousplants.ansci.cornell.edu]

  The patient may feel tired, feverish, or experience a headache, and the condition can also cause abdominal pain, nausea, and vomiting. If left untreated, it can result in serious health problems, like a coma. [wisegeekhealth.com]

  Nausea, abdominal pain and diarrhea may develop. Vomiting only occurs rarely. Within 6 to 24 hours, urine may become noticeably dark and can appear red, brown or even black. [rarediseases.org]

  Sensitive individuals suffer from acute hemolytic anemia upon exposure with characteristic symptoms that include pallor, fatigue, dyspnea, nausea, abdominal and/or back pain, fever, and chills. [farrp.unl.edu]

• Tachycardia

  Cardiac tamponade presents with dyspnea, tachycardia, elevated jugular venous pressure, and pulsus paradoxus. [15] The gold standard for diagnosis is ultrasound. [15] Anaphylaxis typically begins over a few minutes in a person with a previous history [en.wikipedia.org]

  Affected children may become pale and their resting heartrate may be high (tachycardia). Jaundice can also develop and the liver and spleen may become enlarged. [rarediseases.org]

• Jaundice

  Abstract Jaundice and bilirubin levels varied widely in 85 children with favism. [ncbi.nlm.nih.gov]

  It is common for babies to have jaundice in the first week of life, but some babies with G6PD deficiency have jaundice for longer than usual. When to see a doctor Newborns with persistent jaundice may have a blood test to look for G6PD deficiency. [rch.org.au]

  Jaundice. Patients with G6PD deficiency are prone to gallstones and splenomegaly due to recurrent, often subclinical, episodes of haemolysis. [patient.info]

  Rat fever ( leptospirosis ) can also cause hepatic jaundice. In hepatic jaundice, there is invariably cholestasis. [en.wikipedia.org]

• Neonatal Jaundice

  There was no family history of favism or neonatal jaundice. The baby received transfusions and the parents were advised about the food and drugs to be avoided. After 8 weeks, his hemoglobin improved to 140 g/L. [bloodjournal.org]

  Neonatal jaundice Other names Neonatal hyperbilirubinemia, neonatal icterus, jaundice in newborns Jaundice in a newborn Specialty Pediatrics Symptoms Yellowish discoloration of the skin and white part of the eyes [1] Complications Seizures, cerebral palsy [en.wikipedia.org]

  Types The severe Mediterranean type of G6PD deficiency has been associated with severe neonatal jaundice and favism. [ourmed.org]

• Night Sweats

  Diagnosis of leukocytes is initiated by the presence of clinical symptoms such as fever, night sweats, weight loss, and abnormal bleeding. However, history of previous disease, smoking, and infection is also significant in this case. [onlinelibrary.wiley.com]

• Dark Urine

  The urine is dark and full of hemoglobin, and the level of unconjugated bilirubin in the serum is very high. “The parents, if asked, almost always report that their son has dark urine and has eaten fava beans.” [hematology.org]

  Case Presentation: A 43 year old Albanian man without any significant past medical history, presented to the hospital with sudden onset intermittent dyspnea, chills and dark urine of 4 days duration. [shmabstracts.com]

  Early warning signs include jaundice, dark urine, and a general sense of feeling run down and tired all the time. People who think that they may have favism can be tested for it. [wisegeekhealth.com]

  The major symptoms of hemolytic anemia are jaundice, dark urine, abdominal pain, back pain, lowered red blood cell count, and elevated bilirubin. [encyclopedia.com]

  Most prominent symptoms include weakness, headaches, pallor, abdominal pain, dark urine due to hemoglobinuria and in some cases jaundice. [symptoma.com]

Patients with favism require a thorough diagnostic workup, including CBC, reticulocyte count, haptoglobin, bilirubin levels, blood urea nitrogen (BUN), creatinine, urinalysis (with a particular emphasis on hemoglobinuria and proteinuria), liver function tests (alanine and aspartate aminotransferases - AST and ALT) and lactate dehydrogenase (LDH). Laboratory tests will show low levels of hemoglobin and often high reticulocyte count, together with raised indirect bilirubin, while abdominal ultrasound may be useful in excluding splenomegaly which may be suspected during the physical examination. In all patients, a G6PD assay should be performed, to confirm the presence of G6PD deficiency. A vital component in establishing the diagnosis of favism is patient history, which may reveal key information regarding recent consumption of fava beans and provide key pieces in establishing the diagnosis early on.

• Heinz Bodies

  Moreover, exposure of intact RBC to 20 mmol/L APH induced depletion of procalpain activity for which the time course was inversely related to formation of Heinz bodies. [ncbi.nlm.nih.gov]

  Heinz bodies and Bite cells are characteristic of these cases but their absence does not exclude the diagnosis. Methylene blue should not be used to manage Methemoglobinemia in diagnosed or suspected G6PD deficiency. [shmabstracts.com]

  The cross-linked hemoglobin forms what is referred to histologically as Heinz bodies. [themedicalbiochemistrypage.org]

  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. [en.wikipedia.org]

• Haptoglobin Decreased

  G6PD deficiency and associated acute hemolysis Back pain Complete blood count Mild to severe anemia Abdominal pain Reticulocyte count Increases four to seven days after hemolysis Jaundice Peripheral blood smear Heinz bodies Transient splenomegaly Haptoglobin [aafp.org]

  Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency. [en.wikipedia.org]

Supportive treatment is the mainstay of managing patients with favism. Because patients may deteriorate rapidly, immediate transfer to intensive care upon admission should be considered. Basic measures include maintenance of blood pressure and kidney perfusion through correction of fluids and electrolytes and preservation of adequate ventilation as well as oxygen saturation. In the case of hemoglobinuria, iron supplementation may be useful in restoring hemoglobin levels. The use of folic acid may be recommended as well. In severe cases when hemolysis is significant, blood transfusions may be indicated, but iron supplementation should be closely monitored, as it can lead to iron overload. High-dose vitamin E has been recommended according to certain studies [15], but its effects remain controversial.

The prognosis may be correlated with the severity of G6PD deficiency, since various forms of favism, including mild, moderate and severe anemia have been mentioned in literature [11]. With adequate supportive treatment, the prognosis is generally good, but favism may cause life-threatening symptoms and complications, such as kidney failure and result in significant morbidity [12]. A prompt diagnosis and appropriate treatment may be life-saving.

Favism occurs as a result of either ingestion of fava beans or inhalation of pollen from the fava plant, Vicia faba. This condition is almost exclusively diagnosed in patients with G6PD deficiency, a type of hemolytic anemia in which insufficient production of GSH leads to accumulated free-radical mediated oxygen stress. Presumably, certain substances located inside fava beans, with vicine and convicine being the most prominent candidates, induce oxidative injury in the erythrocytes that cannot be surmounted in G6PD patients because of GSH deficiency. Other theories include infectious pathogens as possible causative agents, due to very rare recurrence of symptoms, as well as most frequent appearance among the pediatric population in a seasonal fashion [2]. Immune mechanisms have also been hypothesized to play a role in the development of favism, including the complement system and anti-band-3 antibodies and their respective roles in the mediation of oxygen-induced stress in erythrocytes [3]. However, the exact cause, as well as, the mechanisms of the disease remain unknown.

Because favism is almost exclusively diagnosed in patients with G6PD deficiency, and also because of the cultivation of fava beans, countries of the Mediterranean region report the majority of cases [4]. Favism is most commonly diagnosed in children between 1-5 years of age with G6PD, while cases of favism in adults have been infrequently reported. Because G6PD is inherited via the X chromosome, virtually all patients with favism are males [4]. The majority of cases occur during spring and during harvesting of fava beans, while inhalation of fava pollen is also a known mode of the disease [5]. In very rare cases, neonatal favism due to consumption of fava beans by mothers prior to delivery may occur [6], while some studies established lactation as a mode of transmission of toxic substances after recent fava bean ingestion.

It is reported that all patients in whom ingestion of fava beans produces symptoms are G6PD deficient and that the pathogenesis invariably involves this genetic condition [7]. G6PD is an essential constituent in the synthesis of glutathione peroxidase (GSH), one of the most important enzymes in battling oxidative stress in many cells, including erythrocytes. In the setting of G6PD deficiency, red blood cells are not able to sustain free radical injury. Hydrogen peroxide, one of the more potent free radicals generated in erythrocytes, targets primarily globin chains, which oxidize and damage the cell wall. Eventually,there is mild damage to erythrocytes with subsequent splenic degradation, but the end-result is diffuse hemolysis. In patients with favism, substances that have been hypothesized to induce such changes include vicine and convicine and their biologically active forms, divicine and isouramil, respectively [8]. Supposedly, these substances induce oxidative stress within erythrocytes [9], but further evidence is necessary to confirm the exact mechanism of damage. Animal models have shown evident hematotoxicity of these substances [10].

Since the introduction of screening for G6PD deficiency in certain countries, markedly reduced rates of favism have been observed, which indicates that screening programs may significantly aid in reducing the burden of favism in medical practice and everyday life [16]. These studies have also shown that there is an increasing incidence of favism in female patients, suggesting the involvement of other factors in the pathogenesis of this syndrome. However, an increased awareness of this disease among patients at-risk has been achieved [16]. For these reasons, screening can be initially targeted at individuals with known family history for this X-linked genetic disease. On the other hand, avoidance of fava bean consumption has been recommended as a form of prevention. Certain studies have discovered that favism usually occurs in patients when ingesting fava beans accidentally or for the first time. This may be the reason why the majority of patients are young children.Interestingly recurrence of symptoms with repeated fava bean ingestion is rarely observed. This questions the role of avoiding fava beans as a preventive strategy [2].

Favism is a condition characterized by the development of hemolytic anemia after ingestion of fava beans and it is almost exclusively seen in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency impairs production of anti-oxidative enzymes such as glutathione peroxidase (GSH) and occurs as a result of mutations in the X chromosome [1]. This syndrome predisposes individuals to favism presumably because fava beans contain several substances that induce oxidative stress inside erythrocytes, with vicine and convicine being the most recognizable toxins. Uncontrolled intraerythrocytic oxidative stress leads to red blood cell hemolysis and anemia. However, the exact pathogenic mechanisms of red blood cell damage and actions of the toxins that cause this phenomenon remain unknown. Infectious pathogens, as well as immune-mediated mechanisms, are thought to be a contributing factor[2]. The mode of G6PD transmission implies an almost total predominance of male patients. Countries around the Mediterranean report a high incidence of cases as they have both: fava bean consumption and high prevalence rates of G6PD deficiency. Most commonly, favism is diagnosed in children, but patients of any age may be affected. Because of the disease mechanism, anemia is the main clinical feature, while other accompanying symptoms may include fever, headache, weakness and appear approximately 1-2 days after eating fava beans [2]. Symptoms may last up to 5 days and can range from mild to severe [2]. Since no specific tests exist for the diagnosis of favism, patient history is the most important component in the diagnostic workup and all patients should be evaluated for G6PD deficiency, if not diagnosed already with this disease. Laboratory workup should include a complete blood count (CBC), serum electrolytes, as well as kidney and liver function tests since favism has been documented as a cause of renal failure. Treatment includes management of symptoms, while prevention strategies could include avoiding fava beans in patients with known G6PD deficiency. However, symptoms rarely recur with repeated ingestion of fava beans, which further brings into question the exact etiology of the disease.

Favism is an illness that occurs after ingestion of fava beans. In virtually all cases, favism occurs in patients with an inherited disease called glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is most commonly seen in the countries around the Mediterranean. This genetic disorder is characterized by the impaired function of enzymes that are involved in the production of substances that should regulate free-radical damage of cells, primarily in the red blood cells. G6PD is an important factor in the synthesis of glutathione peroxidase (GSH), one of the main enzymes involved in reducing the number of active free radicals. The exact sequence of events in favism is not entirely known, but it is assumed that certain substances located inside the fava beans induce significant free-radical mediated injury of red blood cells, which cannot be stopped due to deficient levels of GSH, ultimately leading to their damage and rupture, thus causing anemia. This genetic disease is transmitted via the X chromosome, meaning that males are much more frequently affected. In addition to ingestion of fava beans, inhalation of pollen from the fava bean plant (Vicia faba) has also been established to be a mode of disease. The main clinical feature of patients with favism is the appearance of symptoms such as pallor, abdominal pain, weakness and severe anemia 1-2 days after ingestion of fava beans. Symptoms may be mild, or they may be severe and life-threatening, which necessitates rapid diagnostic workup and appropriate therapeutic measures. Since the exact diagnosis cannot be established by laboratory tests, patients should be asked for recent fava bean consumption, while a detailed workup should include a complete blood count (which will reveal anemia and increased count of immature red blood cells, known as reticulocytes) and evaluation of kidney and liver function, since many patients may excrete hemoglobin through urine (hemoglobinuria). All patients should be tested for G6PD deficiency since this disorder is termed to be a necessary component in the development of favism. Treatment primarily includes supportive measures such as maintaining adequate blood pressure and breathing, correction of serum electrolytes and fluid imbalance to prevent kidney damage, while blood transfusions may be necessary in severe cases. Significant steps in prevention can be made by the screening of family members with G6PD deficiency. Avoiding fava bean consumption in these patients is strongly recommended.

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