A multidisciplinary approach to treatment of Fabry disease is recommended.
To manage the clinical manifestations associated with Fabry disease, symptomatic treatment and supportive care can be provided in addition to Fabry disease-specific therapy, if indicated.1 Several publications in the medical literature contain recommendations regarding adjunctive support for the management of paediatric and adult Fabry disease symptoms. An overview of the published recommendations are provided in Figures 1and2.1,2The availability of treatments may differ between countries. For further information, please consult your local prescribing information and national guidelines for symptomatic management of Fabry disease-related symptoms.
Paediatric patients
It is recommended that pain management be individualised in children with Fabry disease; non-opiates, such as antiepileptics, tricyclic antidepressants and serotonin–noradrenaline uptake inhibitors may be used. Children with Fabry disease-associated pain can initiate treatment on low-dose monotherapy and be slowly titrated up to the maximum dose, depending on pain levels. If monotherapy is ineffective after several weeks, different pain medication may be added. It is recommended that long-term use of pain therapies should be avoided in children due to neurological side effects.2 The analgesic effect of opiates for managing chronic neuropathic pain is considered uncertain and is associated with adverse events.5
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be used to treat pathological proteinuria in children with Fabry disease.2,3
Healthy lifestyle measures and healthy eating can be encouraged in children with Fabry disease to avoid cardiovascular disease in adulthood. Blood pressure and dyslipidaemia may also be monitored.2
Prevention of vitamin and iron deficiencies in children with Fabry disease may be accomplished with dietary measures.2 Dietary restrictions and small, frequent meals may also aid gastrointestinal symptoms.2,3
A diagnosis of Fabry disease in children can be a difficult process emotionally for both the patient and their family.2 Children with Fabry disease may experience anxiety and depression if they are unable to participate in games and sport due to pain or overheating.2,4,6 Challenges associated with Fabry disease may also lead to school absenteeism and reduced academic performance. An annual assessment of quality of life and school attendance and performance is recommended; children experiencing difficulties may benefit from a referral to a psychologist or social worker for support.2
Figure 1.
Suggested adjunctive support for management of paediatric Fabry disease. Reproduced with permission from Germain DP et al. Clin Genet 2019; 96: 107-117.2-6
Adult patients
Support and counselling, including genetic counselling, is recommended throughout the process of diagnosis, investigation and therapy for patients with Fabry disease and their families.1,7
The standard approach to management of chronic kidney disease is recommended for patients with Fabry disease. In patients exhibiting early stages of renal impairment, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can be used to target albuminuria levels <30 mg/g creatinine if baseline levels are 30‒300 mg/g, or target albuminuria levels <300 mg/g creatinine if baseline levels are >300 mg/g. Albuminuria levels >300 mg/g are approximately equivalent to proteinuria >500 mg/g. Use of these treatments should be used with caution in patients with baseline hypotension; dietary salt restriction may also be recommended in this group of patients with Fabry disease.1
Relevant guidelines should also be followed regarding use of statins and chronic kidney disease–mineral and bone disease prevention and management.1,8,9 Replacement therapy for 25-hydroxy vitamin D deficiency may be considered, if relevant, for patients with Fabry disease-related symptoms.1,9 For patients with Fabry disease who are at risk of renal failure, either dialysis or kidney transplantation may be possible if a donor relative has screened negative for Fabry disease.1
Patients experiencing chest pain may be treated with anti-angina medication, such as calcium antagonists or nitrates.10 Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may also be used if patients experience cardiac symptoms related to Fabry disease. Caution is advised with the use of beta blockers, which requires careful monitoring due to the risk of bradycardia exacerbation and chronotropic incompetence. As highlighted in Ortiz et al. Mol Genet Metab 2018, it is recommended that patients with Fabry disease who are receiving enzyme replacement therapy should avoid treatment with amiodarone. Treatment with amiodarone in patients with Fabry disease should be limited in general, as it may have an inhibitory effect on alpha-galactosidase A (α-Gal A) activity.1*
A permanent cardiac pacemaker is a consideration for patients with Fabry disease if there is evidence of symptomatic bradycardia, chronotropic incompetence or significant atrioventricular conduction impairment. Initiation of lifetime coagulation therapy may be considered if patients exhibit atrial fibrillation; maintenance of sinus rhythm is preferred in this patient group, while administration of amiodarone should be avoided if possible. An implantable cardioverter defibrillator can be considered for patients with Fabry disease if there is evidence or a strong suspicion of malignant arrythmias.1 For patients experiencing heart failure, use of diuretics, angiotensin-converting enzyme inhibitors and digoxin is recommended.10
*Based on the Summary of Product Characteristics (SmPC), as approved by the European Commission, agalsidase alfa and agalsidase beta should not be administered with amiodarone, benoquin, chloroquine or gentamycin due to a theoretical risk of inhibition of intracellular α-Gal A activity.12,13
Antithrombotic agents, such as aspirin or clopidogrel, can be used as secondary preventative measures for stroke prophylaxis in patients with Fabry disease.1,3 No data are currently available for primary prevention of stroke in patients with Fabry disease. An anticoagulant, such as warfarin, is also recommended as needed for stroke prophylaxis.1
It is recommended that pain management of neuropathic pain in patients with Fabry disease be individualised.1 First-line therapies for neuropathic pain include anticonvulsants (e.g., carbamazepine, gabapentin or pregabalin); however, other drugs can be considered based on current international recommendations for neuropathic pain.1 The analgesic effect of opiates for managing chronic neuropathic pain is considered uncertain and is associated with adverse events.5 Lifestyle modifications are also recommended for avoiding pain triggers. These modifications may include: avoidance of extreme temperatures; maintenance of proper hydration; minimisation of physical exertion and emotional stress; and use of air conditioning, cooling vests or facial mists/sprays.1,10,11
Metoclopramide can be considered for treatment of delayed gastric emptying and H-2 blockers may be used to treat symptoms of dyspepsia. Dietary changes (such as increased fibre intake, and more frequent and smaller meals) and pharmacotherapy may ease dysmotility and diarrhoea in patients with Fabry disease.1
For patients with Fabry disease who exhibit ophthalmological symptoms and have difficulty driving at night, polarised glasses may help manage headlight splaying. Artificial tears ointment may also ease ophthalmological symptoms related to Fabry disease.1
Figure 2.
Suggested adjunctive support for management of adult Fabry disease.1,3,5,7-11
C-ANPROM/INT/FAB/0017; Date of preparation: March 2021
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.
Germain DP, Fouilhoux A, Decramer S, et al. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clin Genet 2019; 96: 107-117.
Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006; 8: 539-548.
Bugescu N, Alioto A, Segal S, et al. The neurocognitive impact of Fabry disease on pediatric patients. Am J Med Genet B Neuropsychiatr Genet 2015; 168B: 204-210.
McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. The Cochrane database of systematic reviews 2013: CD006146.
MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001; 38: 750-760.
Hughes DA, Evans S, Milligan A, et al. A multidisciplinary approach to the care of patients with Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, eds. Fabry Disease: Perspectives from 5 Years of FOS. Oxford, UK: Oxford PharmaGenesis, 2006.
Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney Int Suppl 2013; 3: 259-305.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2017; 7: 1-59.
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.
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.
Should patients with Fabry disease receive support and counselling?
Support and counselling is recommended throughout the process of diagnosis, investigation and therapy for patients with Fabry disease and their families.
