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

Glucose-6-Phosphate Dehydrogenase Deficiency (Favism)

Dr. rer. biol. hum. Katrin Goldmann, Dipl.-Biol. Birgit Busse

Scientific Background

Favism (from Latin: faba = bean) is an X-linked recessive inherited metabolic disorder 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 conversion of glucose-6-phosphate into D-glucono-1,5-lactone 6-phosphate. This results in reduction equivalents such as NADPH that protect certain cell structures (e.g. erythrocyte membranes) from oxidative damage. The cell loses this protective mechanism due to the G6PD deficiency, resulting in hemolytic anemia.

Diverse pathogenic variants in the G6PD gene lead to a G6PD deficiency. The residual enzyme activity and therefore symptom expression varies according to the mutation. G6PD deficiency is categorized according to the measured enzyme activity.

Due to the X chromosomal inheritance, mainly men are affected. Hemizygous men and homozygous or combined heterozygous women with variants on the X chromosome show the fully distinct phenotype. Heterozygous female carriers usually only show symptoms if a preferential expression of the affected allele is present, e.g. due to skewed X-inactivation. The prevalence is 0.14-0.37% among the German population, in some countries in Africa, Asia and the Mediterranean it is 3-35%. In the Western European population, the Mediterranean form caused by the mutation c.563C>T (p.Ser188Phe) is the main cause of favism and leads to a severe course of the disease (WHO class II).

Medication with oxidative action can trigger hemolytic anemic crises and should only be prescribed after a thorough risk-benefit analysis. Fava bean proteins (aglycones) and their pollen can also trigger hemolytic events.

Literature

Belfield and Tichy, Am J Health Syst Pharm 2018 75:97 / Minucci et al. 2009, IUBMB Life, 61: 27 / Turan 2006, Archives of Medical Research 37:880 / Beutler and Vulliamy 2002, Blood Cells Mol Dis 28:93 / Vulliamy et al. 1988, Proc Nat Acad Sci 85:571 / www.favismus.de