Favism

See also: Glucose-6-phosphate dehydrogenase deficiency.

This term describes the susceptibility to, and clinical presentation of, acute haemolytic crises as a result of the ingestion of broad beans, in a subgroup of patients who have glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). It is a potentially life-threatening condition. Broad beans are derived from the plant Vicia fava, hence the condition's name. Susceptible patients may also experience the syndrome when exposed to the plant's pollen.

The condition has been reported to occur only in the mediterranean variety of G6PD deficiency. However, there have been reports of the condition affecting children in Hong Kong,¹ Thailand² and Iran.³ This reflects common ancestry among populations in different parts of the world due to migration, and the large number of genetic polymorphisms that constitute the variable alleles causing G6PD deficiency.²

G6PD is crucial in maintaining red cell homeostasis and its deficiency leads to susceptibility to haemolysis induced by drugs, infections and substances in food. There are a huge number of polymorphisms of the gene with variable effects on the activity of the enzyme and a wide range of phenotypic susceptibility to haemolysis.⁴ The gene for G6PD is located on the X-chromosome,⁴ hence it is an X-linked inherited disease that primarily affects men. It can have clinical effects in homozygous women and a proportion of female heterozygous carriers. It is thought that the susceptibility to favism is determined by a combination of the particular G6PD polymorphism (predominantly the mediterranean form), and by variability in other enzymatic mechanisms, particularly in the metabolism of L-DOPA (found in abundance in broad beans),⁵ and vicine, convicine and isouramil, the so-called anti-nutritional factors that are present in broad beans.⁶

G6PD deficiency is the commonest enzymopathy of man of clinical significance.⁷ It is thought to affect more than 400 million people worldwide.³ The highest prevalence of G6PD deficiency is found in tropical Africa, the Middle East, tropical and subtropical Asia, Papua New Guinea and various mediterranean locations.⁷ Only a proportion of G6PD sufferers are prone to favism, and this proportion is variable between populations. A study in Sardinia, where there is a high prevalence of G6PD deficiency (7.5% of all males are hemizygotes) found 508 cases of favism over a 9-year period.⁸ In a Thai study favism was found in 3.6% of G6PD-deficient children.² It therefore appears to be a relatively rare manifestation of a common genetic polymorphism.

There may be a past history of episodes of neonatal or childhood jaundice. A dietary history may reveal recent ingestion of broad beans. Check for recent medication changes or history consistent with infection. Favism leads to acute, massive intravascular haemolysis. It often affects children of around age 5, as they and their parents are unaware that they have the condition and this is around the age that the child starts to try different foods in the diet.¹ Its main clinical features are:

• Acute back and/or abdominal pain
• 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.

• Acute haemolysis caused by an alternative precipitant in G6PD sufferer (e.g. drugs – particularly antimalarials, infection)
• Sickle cell anaemia and crisis
• Exacerbation of other haemolytic anaemias, e.g. hereditary spherocytosis, autoimmune haemolytic anaemia
• Disseminated intravascular coagulation
• Systemic lupus erythematosus.

• Dipstick urine to reveal evidence of haemoglobinuria
• FBC will show acute haemolytic anaemia picture with low haemoglobin
• Reticulocyte count may be elevated (although often normal in early acute phase)
• Raised indirect bilirubin (unconjugated) indicating haemolysis
• LFTs usually normal
• Serum lactate dehydrogenase may be elevated, indicating haemolysis
• Serum haptoglobins may be low, indicating haemolysis
• Abdominal ultrasound may be used to detect gallstones and/or splenomegaly
• Coombs' test is negative
• G6PD activity assay in undiagnosed cases – may be normal if there is significant reticulocytosis as reticulocytes are rich in the enzyme; assay may need to be repeated in convalescent phase.

• Glucose-6-phosphate dehydrogenase deficiency
• Gallstones due to chronic haemolysis
• Splenomegaly due to chronic haemolysis.

• Avoidance of further ingestion of broad beans
• Folic acid supplementation
• Iron supplementation may be needed in ongoing cases of acute severe intravascular haemolysis
• Oxygen therapy
• Bed rest and transfer to a high care/intensive care setting
• Intravenous fluids to reduce chance of acute oliguric renal impairment¹
• Blood transfusion or exchange transfusion may be needed to treat severe anaemia.¹

• Death due to acute severe haemolytic anaemia (relatively rare)
• Ophthalmological damage due to intra-ocular intravascular haemolysis
• Acute renal failure
• Susceptibility to infection.

This is variable depending on the degree of susceptibility to favism, quantity of beans ingested and access to acute medical care. Most cases do well with supportive care but there is significant morbidity and some mortality associated with the disease.

Avoidance of ingestion of broad beans in patients known to be G6PD deficient, or who have suffered previous episodes of favism. Genetic counselling and screening may be useful where there is a family history of G6PD deficiency, to allow diagnosis before exposure to haemolytic precipitants. Population screening and health education programs in areas of high prevalence of G6PD deficiency have been shown to reduce the incidence of favism in the at-risk population.⁸ See separate article on G6PD deficiency for a list of medications to be avoided in G6PD-deficient patients.