Fabry disease is a complex, multisystemic disorder with a broad range of signs and symptoms. Fabry disease should therefore be considered in the differential diagnosis of many systemic diseases.1 A diagnosis of Fabry disease can be delayed for many years (see misdiagnosis of Fabry disease), because the early disease indicators are often non-specific and there is limited awareness of the disease among clinicians. One of the major challenges in making a correct and timely diagnosis of Fabry disease is its lack of inclusion in a clinician’s differential diagnosis, particularly in young patients (see getting the diagnosis right).2
Genetic testing should be used to confirm a diagnosis of Fabry disease in females and to support a diagnosis in males.3-5 The alpha-galactosidase A (α-Gal A) enzyme assay can be used to diagnose Fabry disease in male patients.3-6 In addition, globotriaosylsphingosine (lyso-Gb3) is considered a useful diagnostic biomarker in some patients with Fabry disease,7-9 and clinical indicators can be used to assess the extent of organ involvement.10 A number of disease severity indexes are also available to assess the severity of Fabry disease.11-15
Once a patient has been diagnosed with Fabry disease, a thorough pedigree analysis is recommended to be performed to identify any family members at risk of the disease.16,17 Family screening for Fabry disease may also identify patients who are at risk of having children with the disease (see prenatal and newborn screening).18
C-ANPROM/INT/FAB/0016; Date of preparation: March 2021
- Kiykim E, Zeybek CAA, Zubarioglu T, et al. Lessons from two cases: is Fabry disease the correct diagnosis? BMJ Case Rep 2015; 2015: bcr2014208150.
- Ellaway C. Paediatric Fabry disease. Transl Pediatr 2016; 5: 37-42.
- Barbey F, Hayoz D, Widmer U, et al. Efficacy of enzyme replacement therapy in Fabry disease. Curr Med Chem Cardiovasc Hematol Agents 2004; 2: 277-286.
- Mehta A. Agalsidase alfa: specific treatment for Fabry disease. Hosp Med 2002; 63: 347-350.
- German Society for Neurology (DGN). Interdisciplinary guidelines for the diagnosis and treatment of Fabry disease. September 2013.
- Gupta S, Ries M, Kotsopoulos S, et al. The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 2005; 84: 261-268.
- Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A 2008; 105: 2812-2817.
- Rombach SM, Dekker N, Bouwman MG, et al. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta 2010; 1802: 741-748.
- Vardarli I, Rischpler C, Herrmann K, et al. Diagnosis and screening of patients with Fabry disease. Ther Clin Risk Manag 2020; 16: 551-558.
- Hughes DA, Aguiar P, Deegan PB, et al. Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative. BMJ Open 2020; 10: e035182.
- Whybra C, Kampmann C, Krummenauer F, et al. The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet 2004; 65: 299-307.
- Hughes DA, Ramaswami U, Barba Romero M-Á, et al. Age adjusting severity scores for Anderson-Fabry disease. Mol Genet Metab 2010; 101: 219-227.
- Whybra C, Bahner F, Baron K. Measurement of disease severity and progression in Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, eds. Fabry Disease: Perspectives from 5 Years of FOS. Oxford, UK: Oxford PharmaGenesis, 2006.
- Giannini EH, Mehta AB, Hilz MJ, et al. A validated disease severity scoring system for Fabry disease. Mol Genet Metab 2010; 99: 283-290.
- Ramaswami U, Stull DE, Parini R, et al. Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ). Health Qual Life Outcomes 2012; 10: 116.
- 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: 555-564.
- 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: 509-514.
- Germain DP. General aspects of X-linked diseases. In: Mehta A, Beck M, Sunder-Plassmann G, eds. Fabry Disease: Perspectives from 5 Years of FOS. Oxford, UK: Oxford PharmaGenesis, 2006.