Genome-wide sequencing may be a great method to discover new rare genetic conditions among children, said investigators from the University of British Columbia. Some kinds of intellectual disability are hard to identify using conventional techniques. New findings were published Wednesday in The New England Journal of Medicine.

The study’s objective was to recognize and discover genetic conditions among patients, in order to find in them a potential treatment, said researchers. They discovered 11 new disease genes and portrayed new symptoms linked to previously known diseases.

Investigators analyzed data from 41 families, which showed signs of intellectual disabilities caused by genetic conditions. 68 percent of participants received a diagnosis and 40 percent were offered targeted treatments.

Genome-wide sequencing may be a great method to discover new rare genetic conditions among children, said investigators from the University of British Columbia. Photo credit: / The Brock Press
Genome-wide sequencing may be a great method to discover new rare genetic conditions among children, said investigators from the University of British Columbia. Photo credit: / The Brock Press

The study may present a promising future for personalized medicine and genetic diagnosis, said Dr. Clara van Karnebeek, principal investigator in the Centre for Molecular Medicine and Therapeutics, at the University of British Columbia and study’s lead author.

“This research is very encouraging because for a subset of patients we can identify the genetic underpinning of their intellectual disability and then determine the right intervention. There’s a bright future ahead for personalized medicine informed by genetic diagnosis.” said van Karnebeek.

Intellectual disabilities are often caused by peculiar genetic conditions

Intellectual disability refers to disorders which cause “limited mental capacity and difficulty with adaptative behaviors”, said the National Institute of Health (NIH). They are developed before the age of 18 and may result from genetic conditions or physical causes such as autism.

For instance, people with intellectual disability may not be able to manage money, routines or socialization, said the NIH. Some kinds of intellectual disability may be linked to genetic conditions that alter metabolic functions of the body to process food, added researchers.

“Metabolic dysfunctions” can lead to a lack of energy and “build-up toxic substances in the brain and body”, said researchers in a press release issued Wednesday, by the Child & Family Research Institute.

Those substances can trigger symptoms such as developmental cognitive delays, epilepsy, and organ dysfunction. Some particular diseases of this kind may answer to treatments “targeting metabolic dysfunction at the cellular level”.

Other treatments include specific diets, vitamin supplements, and bone marrow transplant. If the right treatment is identified, patients can be prevented from brain damage. At the same time, early intervention can enhance cognitive function among children.

Researchers are “changing the paradigm for diagnosing genetic conditions”

A team lead by Dr. Van Karnebeek is interesting in discovering new genetic conditions that may be potentially treated. They have also developed a mobile app, which helps physicians analyze symptoms of patients with intellectual disability.

The new study included patients with neurodevelopmental conditions. Genetic conditions of some patients were not previously identified using conventional methods. All participants were children referred by physicians at BC Children’s Hospital in Vancouver, British Columbia.

Researchers tested children and their parents using a technique called metabolomic analysis. They also used “whole exome sequencing”, which is a type of genomic sequencing. As a result, they were able to study “a portion of DNA that codes for proteins”.

Two new genetic diseases were discovered among 41 families

Researchers reported discovering a new disease called “carbonic anhydrase VA deficiency, which causes “life-threatening sleepiness” and coma due to hyperammonemia. The latter is a metabolic condition which prevents some proteins to convert into energy.

The study found out that a drug called carglumic acid may prevent brain damage among children with carbonic anhydrase VA deficiency. Dr. Van Karnebeek remarked that new findings may be helpful for small percentages of patients with rare genetic conditions.

“Our findings open the door to life-changing treatments for a small yet meaningful percentage of patients. We’re learning more about brain function and the mechanisms underlying intellectual disability. These results are meaningful to individuals who suffer these rare conditions,” said Dr. Van Karnebeek.

Another new metabolic disease called “glutamic oxalo-acetic transaminase 2 deficiency” was also discovered. It causes brain damage, small head size, seizures and developmental delays. Researchers found that symptoms were reduced with vitamin B6 and a drug called serine.

Understanding the human genome

“Understanding the human genome is similar to having all the pages of a manual needed to make the human body,” says the NIH

On April 203, researchers at the Human Genome Project were able to sequence the human genome for the first time ever. It contains all “the genetic instructions needed to develop activities” of every living thing, said the National Institutes of Health (NIH).

Within the next decades, researchers will be working to better understand the role that genes play in health and pathology of human disease, said the NIH. Genetic diagnosis tools are creating a new field of “personalized medicine”, which helps people according to their genetic needs.

Genome-wide sequencing may be also a great method for preventing disease worldwide. For instance, results from the study lead by Dr. Van Karnebeek may help some patients from developing brain damage.

Source: Child & Family Research Institute Press Release