When should a nephrologist suspect Fabry disease?
The information on this page is tailored for nephrologists. For more detailed information on the cause, inheritance, diagnosis and management of Fabry disease, please refer to our ‘About Fabry disease’ page.
Renal signs in Fabry disease
The earliest signs likely to be noticed by a nephrologist are proteinuria and albuminuria, both of which worsen over time.1,2 As these signs appear early in the disease course, nephrologists can be instrumental in timely diagnosis and prompt management of Fabry disease.
It is also important to consider those patients who are in the early stages of, or who already have a diagnosis of chronic kidney disease (CKD), a condition with estimated prevalence of 15% in all people aged ≥35 years in England.3 Most diagnoses are dependent on standard office work-up and sometimes biopsy findings. However, early stage CKD is frequently clinically silent, and the precise cause remains unknown in many patients. Recent genetic diagnostic testing identified genetic disorders in 23% of a cohort of patients with previously undiagnosed or familial CKD.4 Rare genetic disorders such as Fabry disease could be considered when diagnosing CKD, especially in the early stages.
Besides this, presence of any of the following should lead you to consider Fabry disease:
- GL–3 accumulation in glomerular endothelial, mesangial and interstitial cells
- Glomerular sclerosis, tubular atrophy, interstitial fibrosis (may lead to renal failure)
- Decreased GFR (Glomerular Filtration Rate) and progressive renal failure
- Renal biopsy demonstrating renal damage
- Podocyte foot process effacement
This table outlines the prevalence of Fabry disease from studies in patients on renal dialysis.
|Saito et al., 20156||8547 patients (63% male) on dialysis in Japan||0.04% in males, 0% in females|
|Herrera et al., 20147||3650 patients (61% male) on dialysis in Spain||0.18% in males, 0.49% in females|
|Merta et al., 20078||3370 patients (45% male) on haemodialysis in the Czech Republic||0.26% in males, 0.05% in females|
Damage to both the heart and the kidneys in Fabry disease may lead to ‘cross-talk’ and development of secondary cardiorenal syndrome, often with insidious onset. However, this is a very late sign of Fabry disease.9
Identifying symptoms beyond renal impairment is critical to establishing a diagnosis. Non-renal manifestations may include:1
ECG abnormalities (shortened PR interval, arrhythmia), angina, myocardial infarction, LVH, heart failure
Acroparaesthesia, pain crises, neuropathic pain; pain is a common early symptom of Fabry disease, often beginning in adolescence
Abdominal pain (often after eating), nausea, vomiting
Cornea verticillata, retinal tortuosity
Angiokeratoma and dyshidrosis
Ultimately, referral to nominated ultra-specialist centres is required so that patients can access full genetic testing and access to disease-specific therapies.
This map displays the centres that specialise in the testing and management of Fabry disease.
Tap on each pin on the map to learn more.
- Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.
- Hirst JA, Hill N, O’Callaghan CA, et al. Prevalence of chronic kidney disease in the community using data fom OxRen: a UK population-based cohort study. Br J Gen Pract. 2020;70:e285–293.
- Lata S, Marasa M, Li Y, et al. Whole-exome sequencing in adults with chronic kidney disease a pilot study. Ann Intern Med. 2018;168:100–109.
- Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. Q J Med. 2010;103:641-59.
- 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.
- Saito O, Kusano E, Akimoto T, et al. Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST). Clin Exp Nephrol. 2015;20:284–293.
- Herrera J & Sa Miranda C. Prevalence of Fabry’s disease within hemodialysis patients in Spain. Clinical Nephrology. 2014;81:112–120.
- Merta M, Reiterova J, Ledvinova J, et al. A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population. Nephrol Dial Transplant. 2007;22:179–186.
- Sharma A, Sartori M, Zaragoza JJ, et al. Fabry’s disease: an example of cardiorenal syndrome type 5. Heart Fail Rev. 2015;20:689-708.
Renal pathophysiology in Fabry disease
Management of Fabry disease