Scientists explain genetic disease first discovered in Quebec 24 years ago

Scientists at the MUHC and McGill University have identified a gene essential for the uptake of vitamin B12 in human cells.

The discovery of this gene finally completes a 24 year-old hunt for the cause of an incredibly rare genetic disorder called, cblF combined homocystinuria and methylmalonic aciduria (cblF-Hcy-MMA), first documented in a Quebec infant in 1985. The work, which was funded in part by the CIHR and involved collaboration among researchers in Canada, Germany, Switzerland and France, was published online in Nature Genetics this week.

Two contrasting approaches combined to crack the genetic puzzle at the heart of cblF. In Germany, Dr. Frank Rutsch and his colleagues used DNA from patients to conduct a genome scan for shared regions of DNA sequence. Simultaneously in Montreal, Isabelle R. Miousse, a graduate student of Dr. David Rosenblatt – Chairman of Human Genetics and Director of the Division of Medical Genetics in Medicine at McGill – conducted research that confirmed a gene on chromosome 6 could correct the cellular defect in cells from these patients. Strikingly, the vast majority of patients with this rare disease share a common mutation despite the fact that they come from different countries and different ethnic groups.

"This discovery offers the prospect of earlier diagnosis and treatment options for this disease," says Dr. Rosenblatt, who was the first to describe this rare genetic condition in 1985. "Vitamin B12 plays an important role in our lives," says Dr. Rosenblatt. "Studying rare genetic diseases like cblF-Hcy-MMA offers a window into its basic properties and how it behaves in healthy cells."

The cblF idisease is a rare genetic disorder characterized by an inability to metabolize vitamin B12. Patients afflicted with this condition build up toxic levels of homocysteine and methylmalonic acid in their bodies. Vitamin B12, which is found in all animal products-including dairy, eggs, meat, poultry, and fish, is vital for the synthesis of red blood cells and the maintenance of the nervous system. It also helps control homocysteine levels in the human body, an excess of which is associated with an increased risk of heart disease, stroke and dementia.