Fabry disease revisited: Management and treatment recommendations for adult patients

Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the "classic" phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.

Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients

“…In general, existing guidelines recommend ERT initiation for all patients at the time of symptom onset 35,36 or organ involvement. 37,78 However, opinion diverges regarding the age of ERT initiation in asymptomatic boys, with recommendations ranging from 8-10 years in the 2016 US guidelines 38 to 10-13 years in the 2006 international guidelines 32 to 16 years in the 2015 European guidelines. 34 During the shortage of agalsidase beta, a European group of experts recommended prioritisation of children for treatment allocation.…”

“…GI involvement is common in children with FD and includes nausea, vomiting, non-specific abdominal pain, constipation, diarrhoea. It is now understood that FD morbidity starts in childhood and worsens with age, and that some girls can have severe disease due to skewed XCI.Numerous studies suggest that early initiation of ERT, even before symptoms appear, can protect organs from damage in later life.In general, existing guidelines recommend ERT initiation for all patients at the time of symptom onset35,36 or organ involvement 37,78. Eating small, frequent meals and dietary restrictions can also help 35.…”

Cardiac phenotype of Fabry Disease

“…В настоящее время разработана генотип-специ-фическая терапия болезни Фабри, направленная на замещение фермента. Фермент-заместительная терапия назначена пациентке на основании послед-них международных рекомендаций [5].…”

Mechanical dispersion in Fabry disease assessed with speckle tracking echocardiography

“…It may occur in different scenarios in the various forms of disease presentation. It may be part of a multisystem disorder in the context of the classic (early-onset) phenotype of the disease, 14 or the heart may be the only affected organ with scarce or no extracardiac involvement (cardiac variant or late-onset variant of FD). 15 Studies have shown that symptoms resulting from cardiac involvement occur in 40%-60% of patients with FD, and although cardiac involvement usually begins in the early stages of life, clinical manifestations appear at about 32 years of age in men and 40 years of age in women.…”