Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Glucose-6-Phosphate Dehydrogenase Deficiency (Favism) [E55.0]

OMIM numbers: 134700, 305900 (G6PD)

Dipl.-Biol. Birgit Busse

Scientific Background

Favism (Latin: faba = bean) is a metabolic disorder with X chromosomal recessive inheritance which is caused by a glucose-6-phosphate dehydrogenase (G6PD) deficiency. The enzyme glucose-6-phosphate dehydrogenase plays a key role in the pentose phosphate pathway and catalyzes the convertion of glucose-6-phosphate into D-glucono-1,5-lactone 6-phosphate. In this process, reduction equivalents such as NADPH are formed, that protect certain cell structures (e.g. erythrocyte membranes) from oxidative damage. The G6PD deficiency causes the cell to lose this protective mechanism, resulting in hemolytic anemia.

Various mutations in the G6PD gene lead to a G6PD deficiency. The remaining enzyme activity and therefore the severity of signs and symptoms vary according to the mutation. The G6PD deficiency is classified into different categories according to the measured enzyme activity.

Due to the X chromosomal inheritance, it is mainly men that are affected. Hemizygous men and homozygous or compound heterozygous women show the full phenotype. Heterozygous female carriers usually only show signs and symptoms if a preferential expression of the affected allele is present, e.g. due to skewed X-inactivation. Among the German population the prevalence is 0.14-0.37%, in some countries in Africa, Asia and the Mediterranean area it is 3-35%. Among the Western European population, the Mediterranean form caused by the mutation c.563C>T (p.Ala188Ser) is the main cause for favism and leads to a severe course of the disease (WHO class II). Oxidatively acting medication may trigger hemolytic anaemic crises and should therefore only be administered after a thorough risk-benefit analysis. The proteins of the fava bean (aglycones) and their pollen trigger hemolytic incidents as well.