See also separate article Glucose-6-phosphate Dehydrogenase Deficiency.

Favism describes the susceptibility to, and clinical presentation of, acute haemolytic crises as a consequence of eating broad beans in a subgroup of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

It can be potentially life-threatening. 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.

G6PD is crucial in maintaining red cell homeostasis and its deficiency leads to increased 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.¹

Genetics

The gene for glucose-6-phosphate dehydrogenase (G6PD) is located on the X chromosome; hence, it is an X-linked inherited disease that primarily affects men.¹ 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),² and vicine, convicine and isouramil (the so-called 'anti-nutritional factors' that are present in broad beans).³

Epidemiology

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy of man of clinical significance.⁴ It is thought to affect more than 400 million people worldwide.⁵
• Only a proportion of G6PD sufferers is prone to favism and this proportion is variable between populations. In a Thai study, favism was found in 3.6% of G6PD-deficient children.⁶ It therefore appears to be a relatively rare manifestation of a common genetic polymorphism.
• The condition had been thought to occur only in the Mediterranean variety of G6PD deficiency. The highest prevalence of G6PD deficiency is found in sub-Saharan Africa, the Middle East, tropical and subtropical Asia, Papua New Guinea and various Mediterranean locations.⁷ However, there have been reports of the condition affecting children in Hong Kong,⁸ Thailand⁶ and Iran.⁵ This reflects common ancestry among populations in different parts of the world due to migration as well as the large number of genetic polymorphisms that constitute the variable alleles causing G6PD deficiency.⁶

Presentation

• 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. 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 glucose-6-phosphate dehydrogenase (G6PD) deficiency are prone to gallstones and splenomegaly due to recurrent, often subclinical, episodes of haemolysis.

Differential diagnosis

• Acute haemolysis caused by an alternative precipitant in the glucose-6-phosphate dehydrogenase (G6PD) deficiency 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.

Investigations

• Dipstick urine testing 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 are 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.
• Glucose-6-phosphate dehydrogenase (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 the convalescent phase.

Associated diseases

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Gallstones due to chronic haemolysis.
• Splenomegaly due to chronic haemolysis.

Management

• Avoid further ingestion of broad beans.
• Folic acid supplementation.
• Iron supplementation if there is ongoing acute severe intravascular haemolysis.
• Oxygen therapy.
• Bed rest and transfer to a high care/intensive care setting.
• Intravenous fluids to reduce the chance of acute oliguric renal impairment.⁸
• Blood transfusion or exchange transfusion is sometimes needed to treat severe anaemia.⁸

Complications

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

Prognosis

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.

Prevention

• Avoidance of ingestion of broad beans in patients known to have glucose-6-phosphate dehydrogenase (G6PD) deficiency, 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.⁹
• See separate article on G6PD deficiency for a list of medications to be avoided in G6PD-deficient patients.

Document references

1. G-6-P-D deficiency, Online Mendelian Inheritance in Man (OMIM), 2006; Genetic detail
2. Favism, Susceptibility to, Online Mendelian Inheritance in Man (OMIM), 1999; Genetic detail
3. Gutierrez N, Avila CM, Duc G, et al; CAPs markers to assist selection for low vicine and convicine contents in faba bean (Vicia faba L.). Theor Appl Genet. 2006 Dec;114(1):59-66. Epub 2006 Sep 30. [abstract]
4. Frank J; Diagnosis and Management of G6PD Deficiency; Am Fam Physician 2005;72(7):1277-82
5. Noori-Daloii MR, Najafi L, Mohammad Ganji S, et al; Molecular identification of mutations in G6PD gene in patients with favism in Iran. J Physiol Biochem. 2004 Dec;60(4):273-7. [abstract]
6. Laosombat V, Sattayasevana B, Chotsampancharoen T, et al; Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children. Int J Hematol. 2006 Feb;83(2):139-43. [abstract]
7. Nkhoma ET, Poole C, Vannappagari V, et al; The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a Blood Cells Mol Dis. 2009 May-Jun;42(3):267-78. Epub 2009 Feb 23. [abstract]
8. Lau HK, Li CH, Lee AC; Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase deficiency. Hong Kong Med J. 2006 Apr;12(2):149-51. [abstract]
9. Meloni T, Forteleoni G, Meloni GF; Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience. Acta Haematol. 1992;87(1-2):29-31. [abstract]

Internet and further reading

• Carter SM et al; Glucose-6-Phosphate Dehydrogenase Deficiency, Medscape, Nov 2009

Acknowledgements