Levels of FGF-21 Protein Could Help Doctors Diagnose Mitochondrial Disease, Study Reports

High levels of the FGF-21 protein may be a better indicator of mitochondrial disease than many currently used diagnostic tools, a study reports.

This is particularly true in adults with chronic progressive external ophthalmoplegia, whose hallmark is weakness or paralysis of extraocular muscles, researchers said. The seven extraocular muscles consist of six that control eye movement and one that controls eyelid elevation. FGF-21’s full scientific name is fibroblast growth factor-21.

The downside of using the protein as a biomarker is that it can generate false positive readings.

Researchers published the study, titled “Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice,” in the Journal of Clinical Medicine.

Diagnosing mitochondrial disease is challenging. One reason is that doctors often have to look at muscle tissue under a microscope, which means doing an invasive biopsy. Other tests, such as respiratory enzyme studies, are difficult to conduct and are available only at specialty centers. Another problem is that the tests can generate false positive readings if tissue is not properly stored and deteriorates.

Even with the tests, doctors often need to do a DNA analysis of a patient before they can make a definitive diagnosis.  All of these steps suggest that doctors would welcome an easier and more accurate method of diagnosing mitochondrial disease.

Recent studies have suggested that levels of FGF-21 in blood serum may have better diagnostic power than standard tests. FGF-21 is a hormone-like molecule that is involved turning carbohydrates and fats into energy.

Scientists have found higher than normal levels of FGF-21 in people with an energy-generating process known as respiratory chain deficiency. Mitochondria are cell components that produce energy, and the process by which they do this is called the respiratory chain.

Previous studies suggested that doctors might be able to use FGF-21 to diagnose mitochondria disease, but no definitive conclusions came out of them. Researchers at Oxford University Hospitals decided to see what would happen if they used FGF-21 as a first-line diagnostic tool for the disease.

Their study covered 155 patients. One hundred four showed evidence of the disease. There were indications that 24 might have the disease, and evidence that 27 did not have it.

The team did a genetic analysis on the patients to determine if they had any mitochondrial DNA mutations.

They discovered that FGF-21 levels were highest in mitochondrial disease patients with DNA maintenance and rearrangement mutations. They found lower FGF-21 levels in patients with single DNA mutations and mutations of genes that are not associated with FGF-21 production. They also found lower levels in those with weaker evidence of mitochondrial disease.

The team discovered a significant overlap in FGF-21 levels between study participants with mitochondrial disease and participants who did not have it. They also looked at other biomarker possibilities, such as high lactate levels —  and found them to be as good if not better mitochondrial disease predictors than FGF-21.

Interestingly, the team discovered that participants with ophthalmoplegia also had higher FGF-21 levels. This indicated that the protein could help doctors diagnose chronic progressive external ophthalmoplegia.

The researchers noted that, at the moment, doctors can use FGF-21 levels to obtain an accurate diagnosis in only about a third of those suspected of having mitochondrial disease. That’s because the biomarker has a tendency to generate false positives.

A major advantage of using the protein as a biomarker would be that in patients with high FGF-21 levels, doctors could skip the muscle biopsy diagnostic test and go right to a genetic analysis, the team said.