Navigation Links
Peering into genetic defects, CU scientists discover a new metabolic disease
Date:9/5/2013

An international team of scientists, including University of Colorado School of Medicine and Children's Hospital Colorado researchers, has discovered a new disease related to an inability to process Vitamin B12.

The disorder is rare but can be devastating.

"Some people with rare inherited conditions cannot process vitamin B 12 properly," says CU researcher Tamim Shaikh, PhD, a geneticist and senior author of a paper about the new disease. "These individuals can end up having serious health problems, including developmental delay, epilepsy, anemia, stroke, psychosis and dementia."

The discovery is important because it could help doctors diagnose the disease and, eventually, could lead to prevention or treatment. But there is more to the story than that.

A 9-year-old Colorado boy named Max Watson, who because of his metabolic disease uses a computer to communicate, was the first patient in whom this discovery was made.

His older sister Abbey, 15, volunteered in the CU lab that helped achieve this medical breakthrough.

His parents cooperated with the study knowing that the results likely would not help their son but might help future patients.

The discovery, published today in The American Journal of Human Genetics, illustrates the complex and relatively new realm of medical discovery where researchers peer into the genetic make-up of patients to discern what went wrong to cause a disease.

Vitamin B 12 also is called cobalamin. The new disease is called cobalimin X, or cblX.

Obtained from foods such as milk, eggs, fish and meat, B 12 is essential to human health because it helps the body convert food into fuel. It's vital to the nervous system and for making red blood cells.

Max was born with symptoms that looked like he had a B 12 problem called cobalamin C deficiency or cblC for short, which, like its newly discovered counterpart, can show up in utero.

The gene for cblC had been discovered by researchers who studied several hundred patients with similar symptoms. A few of those patients, however, did not have the genetic mutation that that was common to the cblC patients. And some, like Max, had symptoms that didn't quite match up.

"We knew from early on that something was unusual about this patient," says Johan Van Hove, MD, a CU professor in the Department of Pediatrics, who saw Max when the boy was just a few months old.

Max was labeled as having cblC but Van Hove and others on a team of metabolism experts at Children's Hospital Colorado had their doubts. Some of Max's symptoms seemed too severe for that diagnosis.

So Shaikh, an associate professor in the medical school's pediatrics department, and CU colleagues, used what is called next generation genetic sequencing to delve into Max's DNA. They also looked at genes of patients who didn't fit the cobalamin C model, obtained from partners at the National Institutes of Health, and in Canada and Switzerland.

All of those patients carried mutations that hadn't been identified before. The problem was due to flaws in a gene designed to control the workings of an enzyme that, in turn, helps the body metabolize B 12. The article gives a name to Max's disease cblX -- because the gene is on the X chromosome.

"This discovery will lead to the correct diagnosis of this serious genetic disorder and will change the way that genetic counseling is given in these families," says study co-author David Rosenblatt, MD, with the Research Institute of the McGill University Health Centre. "It also helps explain how vitamin B 12 functions in the body, even for those without the disorder."

The research moves matters to a new phase, Van Hove says, because "if you have some idea about how the system works, that is the beginning of providing more logical treatment."

The next step, Shaikh adds, "is to determine how mutations in the gene lead to the symptoms seen in patients with cblX in hopes of better understanding the disease and some day being able to head it off or treat it."

For Shaikh, the discovery has meant more than solving a genetic puzzle.

"Laboratory researchers like me don't normally get to meet the people affected by their research. It's been a privilege to meet the Watsons," he says. "They are an amazing family."

When Max's sister Abbey a star athlete -- visited the lab investigating her brother's disease, Shaikh and his team embraced her curiosity and let her join the quest. Max's mother and father, Deana and Steve Watson, grateful to Children's hospital for the care Max received and to CU for leading the research, have done whatever was needed to support the project.

But it hasn't been easy and the discovery doesn't alter Max's condition. Max needs full assistance in all aspects of daily care, including a specialized wheelchair and devices to help him stand and move to a bed. Unable to be in a classroom, he attends school via live internet to the delight of classmates who talk with him on the screen and know his favorite color is yellow.

"We're pretty realistic about all of this," Deana says. "The whole reason we have from the beginning agreed to any sort of studies is that maybe some day, with Max's findings, another family won't be in this situation. We're OK with that and proud Max is playing a part with that."


'/>"/>

Contact: Dan Meyers
dan.meyers@ucdenver.edu
303-724-7904
University of Colorado Denver
Source:Eurekalert

Related biology news :

1. Peering into living cells -- without dye nor fluophore
2. Nearby chimpanzee populations show much greater genetic diversity than distant human populations
3. Will a genetic mutation cause trouble? Ask Spliceman
4. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
5. Perception and preference may have genetic link to obesity
6. A foot in the door to genetic information
7. Genetic survey of endangered Antarctic blue whales shows surprising diversity
8. Epigenetic signatures direct the repair potential of reprogrammed cells
9. Epigenetics and epidemiology -- hip, hype and science
10. Genetic variation in East Asians found to explain resistance to cancer drugs
11. First complete full genetic map of promising energy crop
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/2/2016)... LONDON , June 2, 2016 ... has awarded the 44 million US Dollar project, ... Security Embossed Vehicle Plates including Personalization, Enrolment, and IT Infrastructure ... world leader in the production and implementation of Identity Management ... in January, however Decatur was selected ...
(Date:5/20/2016)... , May 20, 2016  VoiceIt is ... partnership with VoicePass. By working together, ... experience.  Because VoiceIt and VoicePass take slightly different ... engines increases both security and usability. ... excitement about this new partnership. "This ...
(Date:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Global demand for enzymes ... through 2020 to $7.2 billion.  This market includes ... cleaning products, biofuel production, animal feed, and other ... and biocatalysts). Food and beverages will remain the ... increasing consumption of products containing enzymes in developing ...
(Date:6/27/2016)... ... June 27, 2016 , ... Newly created 4Sight ... solutions to the healthcare market. The company's primary focus is on new product ... marketing strategies that are necessary to help companies efficiently bring their products to ...
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/23/2016)... Mass. , June 23, 2016   ... development of novel compounds designed to target cancer ... napabucasin, has been granted Orphan Drug Designation from ... the treatment of gastric cancer, including gastroesophageal junction ... stemness inhibitor designed to inhibit cancer stemness pathways ...
Breaking Biology Technology: