Severe Congenital Disorder Treated Successfully in Mouse Model

Using a mouse model, Heidelberg University Hospital researchers have for the first time successfully treated a severe congenital disorder in which sugar metabolism is disturbed. The team headed by Professor Christian Körner, group leader at the Center for Child and Adolescent Medicine, demonstrated that if female mice are given mannose with their drinking water prior to mating and during pregnancy, their offspring will develop normally even if they carry the genetic mutation for the congenital disorder. The team’s outstanding work will contribute to better understanding of the molecular processes of this metabolic disease, along with the key stages in embryonic development, and may offer a therapeutic approach for the first time. The Heidelberg-based researchers also collaborated with colleagues working with Professor Hermann-Josef Gröne of the German Cancer Research Center (DKFZ)’s Division of Cellular and Molecular Pathology in Heidelberg. Their results were published online on December 11, 2011 in Nature Medicine in advance of their publication in the print edition of that journal. So far, 1,000 children worldwide are affected by congenital disorders of glycosylation (CDG), which are classified as rare diseases. Affecting around 800 children, type CDG-Ia is most frequent. The number of unreported cases is high, however. Children with CDG are severely physically and mentally disabled, with approximately 20 percent dying before the age of two. To date, no therapy has been available to treat the disorder. CDG-Ia is caused by mutations in the genetic information for the enzyme phosphomannomutase 2 which is involved in important glycosylation processes: mannose-1-phosphate is not produced in sufficient quantities.