New Metabolic Disease

Vitamin B12 disorders are rare, but their effects can be devastating. Vitamin B12, also called cobalamin, is necessary for a wide range of functions in the body. People who cannot metabolize it properly have health problems like epilepsy, anemia, stroke, dementia, and developmental delays.

A research team at the University of Colorado (CU) already knew about a genetic disease called cobalamin C (cblC) that causes such symptoms. Out of hundreds of patients with that symptom cluster, though, a few stood out. Their symptoms were more severe and simply didn’t match up.

When Max Watson was born, it was clear that he was one of these outliers. “We knew from early on that something was unusual about this patient,” said Dr. Johan Van Hove, a professor of pediatrics at the University of Colorado School of Medicine, in a press release. Although Max was initially diagnosed with cblC, Van Hove and a team of metabolic experts at Children’s Hospital Colorado wanted to find out more.

Max’s parents, Deana and Steve, agreed to let him be the flagship patient for a genetic study to find the cause of his rare and previously unknown disease.

The research team was joined by Dr. Tamim Shaikh, an associate professor of pediatrics at CU. Together with co-author Dr. David Rosenblatt at the Research Institute of the McGill University Health Centre, he published their discovery.

Cobalamin and the Body

Max has a disorder that Shaikh named cobalamin X (cblX), because the gene that causes it lies on the X chromosome. Genetic problems on the X chromosome, like color blindness and hemophilia, usually only appear in boys, since women have a second copy of the X chromosome to protect against a single bad gene.

“The new disorder we have discovered, cblX, arises due to mutations in a gene that controls the working of one of the enzymes in the [cobalamin metabolism] pathway,” explained Shaikh in an interview with Healthline. “This is the first example of such a mechanism in a metabolic disorder.”

With this discovery, doctors can perhaps learn to manage Max’s condition, as well as help the 14 other people with cblX who have been identified so far. Now that cblX has been discovered and classified, more people who have been misdiagnosed with cblC may be able to get an accurate diagnosis and treatment.

An Answer but Not a Cure

The discovery of this genetic pathway may shed light on other disorders as well. “This discovery teaches us that metabolism is tightly controlled and regulated by other factors in the cells,” says Shaikh. “It is too early to predict the impact of this finding on more common disorders, but it is likely that similar mechanisms will be discovered as the cause of more common disorders, and potential treatment methods may be developed in the future.”

There is no cure yet for cblX, as is the case with most genetic disorders. Max, who is nine years old and in third grade, needs assistance with daily care and a specialized wheelchair. He attends school via live Internet. “Max clearly has many struggles on a daily basis due to his disability, but at the same time his family does an amazing job of maximizing his quality of life,” Shaikh says.

“We’re pretty realistic about all of this,” Deana Watson said in the press release. “The whole reason we have from the beginning agreed to any sort of studies is that maybe someday, with Max’s findings, another family won’t be in this situation. We’re OK with that and proud Max is playing a part.”

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