What Do Blood Test Results Mean in Fabry Disease?
There are various blood tests that doctors can use to diagnose Fabry disease, a progressive genetic disorder caused by a mutation in the GLA gene. It can be confusing for patients and their families to understand what doctors are looking for and what the test results might mean. Here’s some information that should help.
Initially, a combination of signs and symptoms may lead your physician to suspect you have Fabry disease. He may ask you to undergo testing to confirm or disprove his suspicion.
The main blood test your doctor will order is an enzyme assay. It assesses the amount of alpha-galactosidase enzyme activity in your blood. This is the enzyme that is defective in Fabry disease patients. A dried blood spot is sufficient for this test.
Depending on the activity of the enzyme, doctors may diagnose patients with either classic (type 1) or non-classic or late-onset (type 2) Fabry disease. Those with classic Fabry disease typically have enzyme activity below 1%. In people with late-onset Fabry disease, enzyme activity is usually more than 1%.
While doctors also can use this test in female patients, a genetic test is more reliable, particularly if there is no family history of the disease. In fact, such testing is necessary to confirm the presence of the disease in women. This is because Fabry disease is a so-called X-linked disease, when the disease-causing mutation is in a gene located on the X chromosome. Because females have two X chromosomes, they usually have milder symptoms even if they have one X chromosome carrying a faulty gene.
Doctors can use another blood test to gauge the disease’s severity. In Fabry disease, the alpha-galactosidase enzyme functioning improperly leads to the accumulation of a fatty substance called globotriaosylceramide (Gb3). This test looks at the levels of Gb3 in the blood. High levels of Gb3 can efficiently identify both classic and late-onset Fabry disease.
Clinicians can measure the levels of Gb3 using a technique called electrospray ionization liquid chromatography-mass spectrometry. However, not all laboratories provide this niche diagnostic test.
In a study of 38 patients diagnosed with Fabry disease, scientists used the spectrometry assay to determine Gb3 levels in the blood. They determined that a cut-off value of 0.81 ng/mL (nanograms per milliliter) was able to separate patients with Fabry disease from healthy individuals.
Clinicians also can use blood samples for genetic testing. This test seeks out mutations in the GLA gene that are known to cause Fabry disease and may help confirm a diagnosis. There are more than 965 such mutations that doctors know to cause Fabry disease. Mutations in the GLA gene are identified by a complete sequence analysis of the gene.
The most common type of mutation changes a single protein building block — amino acid — in alpha-galactosidase A. Mutations that completely eliminate the activity of the enzyme lead to the severe, classic disease, which typically begins in childhood. Mutations that lower, but do not completely eliminate, the enzyme’s activity usually cause milder, late-onset Fabry disease.
Last updated: Aug. 21, 2020
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