WHEN TO TEST

Darrick, living with Fabry disease

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

Watch Dr. Amy Kritzer discuss with Kira Dineen on the DNA Today podcast why early recognition of the variable symptoms of Fabry disease is essential to improve care

Find out more about

Choosing genetic 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.