From the Guidelines
Screening for Fabry disease should involve a combination of clinical evaluation, laboratory tests, and genetic analysis, with the primary screening test for males being the measurement of alpha-galactosidase A (α-Gal A) enzyme activity in blood, and genetic testing for females due to potential normal enzyme levels despite having the disease. The screening process should begin with a thorough medical history and physical examination, looking for characteristic symptoms such as acroparesthesia, angiokeratomas, corneal whorls, decreased sweating, gastrointestinal issues, and kidney problems 1.
Key Screening Methods
- Clinical evaluation to identify characteristic symptoms
- Laboratory tests:
- Measurement of alpha-galactosidase A (α-Gal A) enzyme activity in blood for males
- Genetic testing for mutations in the GLA gene for females
- Urinary globotriaosylceramide (GL-3 or Gb3) levels as a biomarker
Importance of Early Screening
Early screening is crucial because enzyme replacement therapy (agalsidase alfa or beta) or chaperone therapy (migalastat for amenable mutations) can be initiated to prevent irreversible organ damage, particularly to the heart, kidneys, and brain 1.
Follow-Up and Diagnosis
All patients with Fabry disease should be followed regularly, regardless of disease status or treatment protocols, with annual comprehensive medical evaluations to monitor disease progression and assess the effectiveness of interventions 1. Definitive diagnosis requires genetic testing to identify mutations in the GLA gene, which should be performed in all suspected cases.
From the Research
Screening Methods for Fabry Disease
The following methods are used for screening Fabry disease:
- Measurement of α-galactosidase A activity in blood or dried blood spots 2, 3, 4, 5
- Plasma globotriaosylsphingosine (lyso-Gb3) concentration 2, 3, 4, 5
- Genetic testing (GLA gene sequencing) 2, 3, 4, 5
- Urinary alpha-galactosidase A protein measurement using enzyme-linked immunosorbent assay (ELISA) 6
- Urinary globotriaosylceramide (GL-3) measurement using tandem mass spectrometry (MS/MS) 6
Gender-Specific Screening Algorithms
- For males: measurement of α-galactosidase A activity, followed by genetic testing if activity is low 3, 4
- For females: first-tier testing consisting of GLA sequencing and plasma lyso-Gb3 analysis, with enzyme testing as a second-tier test if necessary 3, 4