Investigators at the University of Calgary and McGill University in Canada
have identified genes that underlie two severe diseases of vitamin B12
metabolism. The two diseases, known as the cblA and cblB forms of methylmalonic
aciduria, may produce brain damage, mental retardation and even death if not
detected in infancy or early childhood.
Melissa Dobson, a graduate student at the University of Calgary working with Roy
Gravel, PhD, is lead author of two papers reporting the identification of the two
genes. The genes were first identified in bacteria and then traced to their human
counterparts. Dobson credits the human genome project with her breakthrough.
“We can now compare human and bacterial DNA sequences to find human genes,” she
stated. “This was made possible by the availability of the sequence of the complete
human genome.”
Methylmalonic acid is a chemical involved in the breakdown of proteins and other
substances. When its metabolism is defective, it accumulates in the body and is
excreted in large amounts in the urine.
Identifying the genes that cause cblA and cblB “will make possible DNA testing for
carriers and early prenatal diagnosis. This is important because treatment can be
started during pregnancy,” said Dr. David Rosenblatt, another McGill University
researcher involved in the study. Many patients can be treated with high-dose vitamin
B12 supplements and a diet that is low in protein.
"This research will lead to better understanding of the disorder and provides hope to
those families living with this disease," added Kathy Stagni, Executive Director of the
Organic Acidemia Association, a nonprofit organization that supports families with
inherited metabolic disorders.
The research is published in the November 26 issue of the Proceedings of the National
Academy of Sciences and the December 15 issue of Human Molecular Genetics. It was
funded by the Canadian Institutes of Health Research (CIHR), the National Institutes of
Health, and the March of Dimes Birth Defects Foundation.
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