The congenital disease favism causes sickness and even jaundice in patients after they consume beans. The culprit is a particular enzyme deficiency, which destroys the red blood cells. Scientists from the University Children’s Hospital Zurich have now discovered that, in the event of a severe or complete enzyme deficiency, patients can also suffer from an immunodeficiency. Patients need to be treated differently depending on the severity of their deficiency.
Favism is a common hereditary disease, affecting around 400 million people worldwide. It is caused by a lack of the enzyme glucose-6-phosphate dehydrogenase (G6PD). This deficiency triggers the destruction of red blood cells (hemolysis) and anemia in patients after they consume fava beans and certain drugs.
In the case of severe forms with a complete enzyme deficiency, life-threatening infections with bacteria and fungi can even occur. However, most specialists who treat these patients are unaware of this. Scientists from the Children’s Research Center at the University Children’s Hospital Zurich and the University of Zurich now reveal the mechanistic link between severe G6PD deficiency and immunodeficiency.
A functioning G6PD enzyme plays a key role in the so-called pentose phosphate pathway in cell metabolism. The co-factor nicotinamide adenine dinucleotide (NADPH) is formed in this process, which has two functions: On the one hand, it guarantees that sufficient glutathione is available in the red blood cells, which protects these cells as an antioxidant.
In the event of a G6PD deficiency, the cells lose this protection against oxidative stress, which results in hemolysis. On the other hand, the co-factor NADPH allows the formation of reactive oxygen compounds in the immune system’s phagocytes that they need to fend off bacterial and fungal infections.
Immunodeficiency similar to septic granulomatosis
The Zurich scientists teamed up with research colleagues from Germany to clarify the mechanism of the defective immune defense in G6PD patients: “In the event of a complete G6PD deficiency, i.e. without any demonstrable residual function of the enzyme, the phagocytes are unable to form any reactive oxygen compounds such as hydrogen peroxide due to the deficient provision of NADPH,” explains Janine Reichenbach, a professor of pediatric immunology at the University of Zurich.
As with a known immunodeficiency in phagocytes called chronic granulomatous disease (CGD), this causes a defective formation of DNA networks – so-called “neutrophil extracellular traps” (NETs), which are needed to capture and kill off bacteria and fungi. “Besides the more minor G6PD deficiency, which chiefly affects red blood cells, a severe or complete enzyme deficiency therefore also constitutes an immunodeficiency in the phagocytes,” says Reichenbach, summarizing the results of the study.
Impact on therapy
This has consequences for the treatment of patients with a G6PD deficiency: “In order to determine the need for permanent antimicrobial prophylactic measures, the severity of the G6PD deficiency has to be determined first during the diagnosis. In the event of a severe enzyme deficiency, the formation of reactive oxygen compounds and DNA networks ought then to be analyzed,” concludes Reichenbach.
Ulrich Siler, Susana Romao, Emilio Tejera, Oleksandr Pastukhov, Elena Kuzmenko, Rocio G. Valencia, Virginia Meda Spaccamela, Bernd H. Belohradsky, Oliver Speer, Markus Schmugge, Elisabeth Kohne, Manfred Hoenig, Joachim Freihorst, Ansgar S. Schulz, Janine Reichenbach, Severe G6PD-deficiency leads to susceptibility to infection and absent NETosis, Allergy and Clinical Immunology, July 22, 2016. DOI: 10.1016/j.jaci.2016.04.041
The University Children’s Hospital Zurich conducts an average of one to two favism analyses per day. One person with favism is usually identified every month.
Favism primarily affects the Mediterranean region, Africa, the Middle East and some Asian countries such as Thailand or India. Its prevalence in Switzerland is less than 0.5 percent (see S. Hofmann et al.; Swiss Medical Forum 2016). Due to migration and travel behavior, however, the number of favism cases in Switzerland could rise in future.
Prof. Dr. med. Janine Reichenbach
Dr. Ulrich Siler
University Children’s Hospital Zurich
Phone: +41 44 635 29 10
University of Zurich
Phone: +41 44 634 44 67
Nathalie Huber | Universität Zürich
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences