When To Test

When to consider testing for Fabry disease

Fabry diagnoses are often delayed for a decade or more due to symptoms that are highly variable and often also associated with other diseases.^1,2 Awareness of Fabry disease and a high index of suspicion are therefore required to diagnose this disorder.^3-5

It is important to be aware that due to the high variability of Fabry disease, patients may exhibit symptoms in multiple organ systems or as few as one.¹

Frequent signs and symptoms of Fabry disease^1,6,7

Cardiac

Impaired heart rate variability; arrhythmias; ECG abnormalities (shortened PR interval); left ventricular hypertrophy; angina; dyspnea¹

Renal

Microalbuminuria, proteinuria; decreased kidney function¹

Neurologic

Neuropathic pain; tingling or burning pain in the extremities; heat and cold intolerance; dyshidrosis (hypohidrosis and hyperhidrosis)^1,7

Dermatologic

Angiokeratomas (dark red spots, typically between the navel and knees)¹

Gastrointestinal

Nausea, vomiting; diarrhea; postprandial bloating and pain; early satiety; difficulty gaining weight¹

Family history

Patients with Fabry disease may have relatives with unexplained kidney failure, heart disease, or other symptoms^6,7

These are not all the possible symptoms of Fabry disease.

A diagnosis of Fabry disease requires confirmation, either¹:

Biochemical testing with an assay for alpha-Gal A enzyme activity

Enzyme activity is informative only in males, as females frequently have enzyme activity within the normal range due to the second GLA allele on their unaffected X chromosome, which makes enzyme activity measurement not useful in females.^1,6

Genetic testing to identify a pathogenic variant in GLA, the causative gene in Fabry disease

Genetic testing to identify a GLA variant provides a definitive diagnosis for males and females.^1,6 It may provide additional information for prognosis, helps define treatment options, and is essential for genetic counseling of family members.^6,8

Find out more about

Choosing tests

Learn about diagnostic strategies

ECG, electrocardiogram; GLA, galactosidase alpha gene.

References: 1. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. 2. Hoffmann B, Mayatepek E. Fabry disease—often seen, rarely diagnosed. Dtsch Arztebl Int. 2009;106(26):440-447. 3. Monda E, Falco L, Palmiero G, et al. Cardiovascular involvement in Fabry’s disease: new advances in diagnostic strategies, outcome prediction and management. Card Fail Rev. 2023;9:e12. 4. Jamboti J, Forrest CH. Fabry disease; early diagnosis improves prognosis but diagnosis is often delayed. J Nephropathol. 2017;6(3):130-133. 5. Gupta A, Luthra SR, Luthra S. Fabry disease in a female: a unique case highlighting the variability in clinical presentation. Cureus. 2024;16(9):e70406. 6. Gal A, Hughes DA, Winchester B. Toward a consensus in the laboratory diagnostics of Fabry disease – recommendations of a European expert group. J Inherit Metab Dis. 2011;34(2):509-514. 7. Laney DA, Bennett RL, Clarke V, et al. Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013;22(5):555-564. 8. Benjamin ER, Della Valle MC, Wu X, et al. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017;19(4):430-438.

WHEN TO TEST