Enzyme Testing for Fabry Disease May Be More Cost-Effective Than Genetic Tests, Study Says

Testing alpha-galactosidase A enzyme activity may be a more cost-effective screening method for diagnosing Fabry disease than genetic tests, a study suggests.

Titled “Cost Efficacy of α-Galactosidase A Enzyme Screening for Fabry Disease,” the study was published in the journal Mayo Clinic Proceedings.

Fabry disease is caused by a lack of the enzyme alpha-galactosidase A. Broadly speaking, there are two ways to test for Fabry if someone is suspected of having the condition. One is to measure the activity of the enzyme in the blood or in blood cells. This can be done relatively cheaply for roughly $100 per test, but it typically doesn’t provide enough information on its own to make a definitive diagnosis.

The other method is genetic testing of the GLA gene, which provides instructions for making alpha-galactosidase A. Results from this type of test are often more informative, although there can be issues when a mutation with an unclear effect is detected. This kind of analysis generally costs much more at about $400 per test.

Hypertrophic cardiomyopathy (HCM) is a heart condition that can mimic the effects of Fabry disease on the heart, although optimal treatment for the two is different. As such, measuring the activity of the alpha-galactosidase A enzyme in individuals suspected of having HCM is a currently used approach, and those with abnormal results are then recommended for additional testing. The researchers wondered whether this was more cost-effective than just testing the GLA gene at the outset.

To find out, they analyzed data for 1,192 patients (528 female, 670 male) with suspected HCM who underwent the routine screening. Of these, 10 had low enzyme activity. Five of these patients (three male, two female) were confirmed to have Fabry disease; notably, genetic testing was only done on three of these (the other two were diagnosed via tissue analysis).

The remaining five were determined to have other conditions without genetic testing. The researchers noted that some of these patients actively chose not to undergo genetic testing, with cost and insurance considerations being common concerns.

Based on these findings, the prevalence of Fabry disease in this group was of 0.42%, which is comparable to what has been found in studies that used genetic testing. This means that there would be one diagnosis per 238 people tested which, assuming $100/test, equates to about $24,000 per diagnosis.

In contrast, if genetic testing was done for all biological females (who are more likely to have Fabry disease), with males continuing to do enzyme testing first, it would cost about $60,000 per diagnosis, assuming the above-mentioned costs and disease frequency, as well as a 50/50 split of the sexes.

Thus, the researchers concluded that, “compared with more comprehensive GLA testing strategies, we identified a similar prevalence of [Fabry disease] at a much lower estimated cost per diagnosis.”