An international team of researchers from Switzerland, the United Kingdom, and Canada has identified the gene responsible for a rare but life-threatening vitamin B12-related disorder. Their findings, published in the New England Journal of Medicine, not only reveal the genetic cause of this condition but also shed light on how vitamin B12 functions within the human body.
The study, conducted by scientists from the University Children’s Hospitals of Basel and Zurich, Brunel University in West London, and McGill University and the McGill University Health Centre (MUHC) in Montreal, uncovered the critical role of the MMADHC gene in vitamin B12 metabolism. Mutations in this gene are responsible for a severe inherited condition known as isolated and combined homocystinuria and methylmalonic aciduria (MMA) of the cblD type. This disorder prevents the body from properly processing vitamin B12, leading to a buildup of toxic substances that cause developmental delays, anemia, and neurological problems such as psychosis.
This discovery builds on earlier work by Dr. David Rosenblatt and colleagues at McGill, who in 2005 identified another gene, MMACHC, linked to a similar metabolic pathway. The latest findings demonstrate that all the symptoms of the cblD-type disorder—though diverse—stem from different mutations within the same gene, offering new clarity into its biological function.
Vitamin B12, a water-soluble nutrient found only in animal-based foods such as meat, eggs, and dairy, is essential for red blood cell formation, nerve function, and maintaining healthy homocysteine levels. Elevated homocysteine is linked to cardiovascular disease, stroke, and dementia. While most people with B12 issues suffer from poor absorption or inadequate dietary intake, individuals with this genetic defect cannot convert the vitamin into its active forms, leading to severe illness.
According to Dr. Rosenblatt, the research underscores the value of global collaboration and the expertise of diagnostic centers in Basel and Montreal. Supported by the Canadian Institutes of Health Research (CIHR), this work not only enables earlier diagnosis and treatment of a devastating disorder but also deepens our understanding of how vitamin B12 supports human health at the molecular level.
Discovery of the Gene Behind a Devastating Vitamin B12 Disorder
