Urine test offers simpler diagnosis for mitochondrial disorders, study finds microbiologystudy

New research at the University of Alberta may make it easier to diagnose serious diseases that disrupt the body’s energy supply.

In a study recently published in Orphanet Journal of Rare Diseases, researchers looked at 297 people with suspected primary mitochondrial disorders to get an understanding of their causes and improve diagnosis and treatment.

An estimated 1 in 5,000 people has a genetic mitochondrial disease. Mitochondria are an essential part of our cells, and when something goes wrong with them, it’s a big problem.

“Mitochondria produce energy for every cell, tissue and organ in our body,” says Anastasia Ambrose, first author of the study. “So if we have variants in our mitochondrial DNA and our mitochondria aren’t functioning properly, it can affect any and every organ.”

“Generally, we expect more problems in those high-energy-requiring organs like our liver, kidneys, skeletal muscle, brain and heart,” says Ambrose, a master’s student in the Department of Medical Genetics. “Those are the big ones.”

There isn’t a cure, but treatment can prevent life-threatening complications, so proper diagnosis as quickly as possible is vital. Unfortunately, these disorders are difficult to identify because there is a lot of overlap with other disorders that have similar symptoms. These can include neuromuscular disorders such as myasthenia gravis and muscular dystrophy.

Ambrose explains that right now, the diagnosis can only be confirmed with molecular genetic testing, and that can be a drain on resources.

“At the Metabolic Genetics Clinic, the most common referral they get is for suspected primary mitochondrial disorders, but most of the time, these patients are not diagnosed with a mitochondrial disorder. This may result in an overuse of genetic testing for a suspected mitochondrial disorder.”

This study was the first to assess mitochondrial DNA testing in urine, which is cheaper and does not involve a muscle biopsy. This means more people with primary mitochondrial disorders can be properly diagnosed more quickly.

The study revealed some differences between how these disorders affect adults and children. Adults are more likely to have a disorder due to errors in mitochondrial DNA in cells, whereas in children the cause is more likely to be nuclear DNA errors in the cells. Researchers also found that muscle problems were more common in adults, and brain and developmental problems were more common in children.

Awareness of these differences can help doctors determine appropriate DNA testing and make specific treatment and management recommendations for children and adults.

“With our study, we were hoping to show the differences between primary mitochondrial disorders and non-PMDs and then give specific recommendations for appropriate genetic tests depending on the age of patients,” says principal investigator Saadet Andrews, a medical genetics professor and member of the Women and Children’s Health Research Institute (WCHRI).

“For example, in children, I wouldn’t recommend doing a muscle biopsy as a first-line investigation if there is a suspected primary mitochondrial disorder, as it is invasive, expensive and requires general anesthesia.”

Ambrose hopes diagnosing these disorders will become easier as a result of their work.

“We are hoping that it helps guide physicians and clinicians in their thinking about who should receive which genetic investigations, and that it can reduce the time it takes for patients to get a diagnosis.”