Skin biopsy offers less invasive diagnosis for mitochondrial disease

Researchers at Children's Hospital Colorado (Children's Colorado) and the University of Colorado Anschutz School of Medicine have published one of the largest studies to date evaluating advanced laboratory testing for mitochondrial disease, providing new evidence that a small skin biopsy can often help diagnose these rare and complex conditions without the need for more invasive procedures.

The study, recently accepted for publication in EMBO Molecular Medicine, evaluated the clinical utility of a comprehensive set of functional diagnostic tests used to identify primary mitochondrial diseases, a group of genetic disorders that impair the body's ability to produce energy. Mitochondrial diseases affect approximately 1 in 5,000 people and can impact multiple organs throughout the body.

The research was jointly led by Johan Van Hove, MD, PhD, clinical biochemical genetics and metabolism specialist at Children's Colorado, and Marisa W. Friederich, PhD, scientific director at Children's Hospital Colorado Mitochondrial Laboratory, who together work on improving the diagnosis for mitochondrial disorders.

Diagnosing mitochondrial disease can be incredibly challenging for patients, families and clinicians. While advances in genetic testing have transformed our ability to identify many of these conditions, a significant number of patients still do not receive clear answers. This study shows that functional testing can play a critical role in closing that gap."

Van Hove, Professor, University of Colorado Anschutz School of Medicine

Genetic testing, including whole genome sequencing, is often the first step in evaluating patients with suspected mitochondrial disease. However, many patients receive inconclusive results because genetic testing identifies variants whose significance is uncertain. In addition, current genetic testing methods identify a definitive genetic cause in only about 50% to 65% of cases.

To help address this challenge, researchers evaluated a broad range of functional tests that measure how well mitochondria perform inside cells. The study assessed how effectively these tests identify mitochondrial disease and distinguish affected patients from those without the condition.

The research included samples from more than 30 medical centers across North America, Europe and Australia/New Zealand, making it one of the most comprehensive evaluations of mitochondrial functional testing conducted to date.

Among the study's most significant findings, researchers demonstrated that cells grown from a small skin biopsy, known as fibroblasts, can often provide the information needed for diagnosis. The findings suggest that more invasive diagnostic procedures, such as muscle or liver biopsies, may not be necessary in many cases.

"For patients and families, reducing the need for invasive procedures is a meaningful advance," said Van Hove. "Being able to obtain critical diagnostic information from a simple skin biopsy has the potential to make the diagnostic process more accessible and less burdensome."

The study was conducted at the University of Colorado Anschutz campus and builds upon years of research and clinical translation. Nearly all of the functional tests examined in the publication are now available through the Mitochondrial Diagnostic Laboratory within the Department of Pathology and Laboratory Medicine at Children's Colorado.

With this expanded testing capability, Children's Colorado has become one of the largest providers of mitochondrial functional testing in North America and receives patient samples from medical centers throughout the United States and Canada.

The publication also represents the first comprehensive evaluation of the clinical performance of these tests, including how often they successfully contribute to a diagnosis and how accurately they identify mitochondrial disease.

Children's Colorado is recognized as one of North America's leading centers for mitochondrial medicine, bringing together a specialized clinical program, diagnostic laboratory, clinical trials and research enterprise focused on improving care for patients with mitochondrial disease.

The study was supported by the National Institutes of Health through the North American Mitochondrial Disease Consortium (NAMDC), as well as funding from the Children's Hospital Colorado Foundation and the University of Colorado Foundation.