INTRODUCING
BURDEN OF DISEASE
Fabry disease is a lysosomal storage disorder caused by variants in the GLA gene and is a progressive, life-threatening, multisystemic condition.
Fabry disease is a rare, multisystemic, lysosomal storage disorder caused by variants in the GLA gene, which is located on the X chromosome. The GLA gene encodes the enzyme alpha-galactosidase A (α-Gal A).1 More than 1000 variants in the GLA gene have been identified, leading to a deficiency of α-Gal A activity (see genetic inheritance of Fabry disease).2-5 In patients with Fabry disease, deficient enzymatic activity of α-Gal A leads to an accumulation of the glycosphingolipids globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) within almost all cell types and various organs (Figure 1).4,6Progressive glycosphingolipid accumulation within cells culminates in the varied disease manifestations of Fabry disease (Figure 2).4,5 Enzymatic activity levels of α-Gal A are somewhat predictive of the classical or late-onset phenotypes of Fabry disease.4 Variants in the GLA gene culminating in little or no enzyme activity (<1%) are associated with classical Fabry disease, whereas patients with residual α-Gal A activity (≥1‒30%) typically develop late-onset Fabry disease.1,7-9 Patients with the classical phenotype usually present with the characteristic symptoms of Fabry disease, whereas for patients with the late-onset phenotype, the disease course may be more variable, and some patients are generally less severely affected; clinical manifestations may also even be limited to a single organ.10,11
Figure 1.
Progression of Fabry disease. Reproduced with permission from Eng CM et al. J Inherit Metab Dis 2007; 30: 184-192.12
Figure 2.
The clinical manifestations of classical Fabry disease are varied.7
The incidence of Fabry disease is estimated to affect approximately 1 in 40,000 males and approximately 1 in 20,000 females.11,13 However, data from newborn screening programmes suggest that the prevalence of Fabry disease is underestimated and is much higher than previously approximated.11,13-19Fabry disease can affect all ethnic, racial and demographic groups.20
Given that Fabry disease is characterised by severe multisystemic involvement, with a wide range of signs and symptoms, this may ultimately lead to major organ failure and premature death.11,21 The age at onset of disease manifestations in males and females with Fabry disease can also vary.21 Consequently, Fabry disease can have a significant impact on patients with many exhibiting a reduced quality of life.22
C-ANPROM/INT/FAB/0015; Date of preparation: March 2021
- Vardarli I, Rischpler C, Herrmann K, et al. Diagnosis and screening of patients with Fabry disease. Ther Clin Risk Manag 2020; 16: 551-558.
- McCafferty EH, Scott LJ. Migalastat: a review in Fabry disease. Drugs 2019; 79: 543-554.
- Tuttolomondo A, Simonetta I, Duro G, et al. Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease. Oncotarget 2017; 8: 61415-61424.
- Schiffmann R, Hughes DA, Linthorst GE, et al. Screening, diagnosis, and management of patients with Fabry disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int 2017; 91: 284-293.
- Felis A, Whitlow M, Kraus A, et al. Current and investigational therapeutics for Fabry disease. Kidney Int Rep 2019; 5: 407-413.
- Brady RO, Gal AE, Bradley RM, et al. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med 1967; 276: 1163-1167.
- Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab 2018; 123: 416-427.
- Clarke JT. Narrative review: Fabry disease. Ann Intern Med 2007; 146: 425-433.
- Michaud M, Mauhin W, Belmatoug N, et al. When and how to diagnose Fabry disease in clinical pratice. Am J Med Sci 2020; 360: 641-649.
- Arends M, Wanner C, Hughes D, et al. Characterization of classical and nonclassical Fabry disease: a multicenter study. J Am Soc Nephrol 2017; 28: 1631-1641.
- Desnick RJ, Ioannou YA, Eng CM. α-galactosidase A deficiency: Fabry disease. In: Scriver C, Beaudet A, Sly W, et al., eds. The Online Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York, NY: McGraw-Hill, 2001.
- Eng CM, Fletcher J, Wilcox WR, et al. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 2007; 30: 184-192.
- Laney DA, Fernhoff PM. Diagnosis of Fabry disease via analysis of family history. J Genet Couns 2008; 17: 79-83.
- Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006; 79: 31-40.
- Colon C, Ortolano S, Melcon-Crespo C, et al. Newborn screening for Fabry disease in the north-west of Spain. Eur J Pediatr 2017; 176: 1075-1081.
- Inoue T, Hattori K, Ihara K, et al. Newborn screening for Fabry disease in Japan: prevalence and genotypes of Fabry disease in a pilot study. J Hum Genet 2013; 58: 548-552.
- van der Tol L, Smid BE, Poorthuis BJHM, et al. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance. J Med Genet 2014; 51: 1-9.
- Scott CR, Elliott S, Buroker N, et al. Identification of infants at risk for developing Fabry, Pompe, or mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry. J Pediatr 2013; 163: 498-503.
- Mechtler TP, Stary S, Metz TF, et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet 2012; 379: 335-341.
- Mehta A, Hughes DA. Fabry disease. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle, 2002.
- Mehta A, Clarke JTR, Giugliani R, et al. Natural course of Fabry disease: changing pattern of causes of death in FOS – Fabry Outcome Survey. J Med Genet 2009; 46: 548-552.
- Arends M, Hollak CEM, Biegstraaten M. Quality of life in patients with Fabry disease: a systematic review of the literature. Orphanet J Rare Dis 2015; 10: 77.
DISEASE MANAGEMENT
STRIVING FOR ORGAN PROTECTION
20 years of treatment for Fabry disease
An interactive video experience
Elearning
SUPPORTING FAMILY CONVERSATIONS:
Family screening for Fabry disease
Family screening is a process to identify any family members at risk of Fabry disease and involves plotting the patient's family tree.
Brochure
STRIVING FOR ORGAN PROTECTION
Fabry Disease: Genetic considerations and pedigree analysis for diagnosis
Following a diagnosis of Fabry disease, it is recommended that a thorough pedigree analysis is performed for each patient to identify any family members at risk of the disease.
Brochure
STRIVING FOR ORGAN PROTECTION
Fabry Disease: Renal considerations for diagnosis
Renal manifestations occur early in the disease course; therefore, nephrologists are recommended to maintain an awareness of Fabry disease.
Events
WORLDSymposium™ 2022
The WORLDSymposium™ was held as a hybrid meeting this year (7–11 February 2022) and brought together key opinion leaders from the field of lysosomal disorders and rare diseases. Here you can access summaries from the meeting, including reports with a specific focus on Fabry disease.
Brochure
STRIVING FOR ORGAN PROTECTION
Fabry Disease: Cardiac considerations for diagnosis
Due to the high prevalence of cardiac involvement in patients with Fabry disease, cardiologists are vital in the screening and diagnosis of the disease. Cardiologists are recommended to maintain an awareness of Fabry disease.
Brochure
STRIVING FOR ORGAN PROTECTION
Fabry Disease: Neurological considerations for diagnosis
Neurologists can aid an early diagnosis of Fabry disease and document neurological involvement associated with the disease.
BURDEN OF DISEASE
Fabry disease
What is Fabry disease?
Fabry disease is an X-linked genetic disorder caused by variants in the GLA gene encoding the lysosomal enzyme α-Gal A.
Burden of disease
Signs and symptoms of Fabry disease
What are the signs and symptoms of Fabry disease?
Fabry disease is a lysosomal storage disorder caused by variants in the GLA gene and is a progressive, life-threatening, multisystemic condition.
BURDEN OF DISEASE
Impact of Fabry disease
What is the impact of Fabry disease?
Fabry disease can have a profound effect on daily activities and quality of life in both paediatric and adult patients.
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