Analysis of dry blood drops may help diagnose Fabry disease and begin early treatment in patients who are experiencing cardiac, renal, or neurological symptoms of unknown cause, according to a recent study.
The diagnostic and risk screening method was proposed by Japanese researchers in the study, “High-risk screening for Anderson–Fabry disease in patients with cardiac, renal, or neurological manifestations,” published in the Journal of Human Genetics.
Fabry disease is a rare genetic disorder that prevents the body from making an enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3) into building blocks that cells can use. The disease is characterized by abnormal sensation and pain affecting hands and feet (acroparesthesias), skin lesions (angiokeratoma), impaired vision, and inability to sweat, as well as vascular problems affecting the heart, kidneys, and brain.
Because it’s rare, affecting one in about 40,000–117,000 people, Fabry disease is poorly recognized by clinicians and can often be misdiagnosed.
“Screening of high-risk populations displaying various cardiac, renal, or neurological manifestations could increase the diagnostic rate of [Fabry disease] and facilitate therapeutic interventions that could prevent serious complications,” the researchers wrote.
Current screening for Fabry disease relies on measuring the levels of alpha-Gal A activity in a specific type of blood cell (leukocytes). In the study, Japanese researchers evaluated the potential of analyzing dried blood spots, collected with a small pinch and stored in paper, to efficiently screen patients at risk for Fabry disease and thereby improve early diagnosis.
The team collected dried blood samples from a total of 2,325 patients, with median age of 66 years, who had various cardiac, renal, or neurological symptoms.
Among the patients, 63% were undergoing hemodialysis, 26% had left ventricular hypertrophy (enlarged ventricles in the heart), 16% had high levels of protein in the urine, 11% have had a stroke, and 18% had typical symptoms of Fabry.
Using the dried blood samples, the team evaluated the activity of alpha-Gal A. The mean alpha-Gal A activity was 24.2 in women and 24.5 Agal U in men. In particular, 410 patients had alpha-Gal A activity values consistent with low enzymatic activity: 333 women (20 Agal U) and 77 men (12 Agal U).
A second activity analysis of these 410 patients — this time using new dried blood samples — confirmed the low values detected in the first test in 92 patients (80 women and 12 men).
Samples from these 92 patients were then analyzed for mutations in the GLA gene, which are seen in individuals with Fabry disease. Six patients (0.26% of all participants) were confirmed to carry disease-associated GLA mutations.
Supported by these results, the team believes that “this simple diagnostic test” of using dry blood samples can be an effective high-risk screening system for specialists and general physicians to identify patients with Fabry disease.