Search

Introduction Published data on hypertension incidence and management in Anderson–Fabry disease are scant and the contribution of elevated blood pressure to organ damage is not well recognized. Aim Therefore, we have assessed blood pressure values and their possible correlations with clinical findings in a well described cohort of Fabry patients. Methods Between January 2015 and May 2019, all adult Fabry patients (n = 24 females, n = 8 males) referred to our institute were prospectively enrolled. During the first examination patient’s genotype and clinical characteristics were recorded. Blood pressure data were obtained by standard observed office measurements followed, within 6 months, by ambulatory blood pressure monitoring and home self-recordings. Organ involvement, including kidneys, heart and brain, was monitored over time. Consequently, patients were defined as clinically stable or progressive through the Fabry Stabilization Index. Results The standard office measurements have diagnosed hypertension in three (9.37%) patients, but the ambulatory monitoring showed elevated blood pressure in six (18.75%) patients, revealing three cases of masked hypertension. All the hypertensive patients were females and, compared with normotensive subjects, they presented a lower glomerular filtration rate (p < 0.05) and a more advanced cardiac hypertrophy (p < 0.05). Four (66.7%) of them were diagnosed with a progressive form of the disease through the Fabry Stabilization Index while the majority of the normotensive group (84.6%, n = 19) was stable over time. No correlation was found between the prevalence of hypertension and the type of mutations causing Fabry disease. Conclusion Hypertension can be found in a restricted portion of clinically stable Fabry patients. In contrast, patients presenting with a progressive organ involvement, particularly renal impairment, have a major risk of developing uncontrolled blood pressure, and should be followed carefully. Moreover, the ambulatory blood pressure monitoring proved to be useful to reveal masked hypertension, which can contribute to the progressive worsening of the organ damage. Therefore, a proper diagnosis and therapy of hypertension may improve the outcome of Fabry patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40292-021-00450-0.

We present the case of a 76-year-old man with late-onset Fabry disease caused by the p.N215S missense mutation, with Fabry cardiomyopathy and nephropathy. In this case, the diagnosis of Fabry disease was incidental and followed minimal change disease (MCD) onset, with nephrotic syndrome and acute kidney injury requiring renal replacement therapy. Fabry nephropathy associated with the p.N215S mutation is becoming increasingly recognized among older patients. The importance of electron microscopy is herein highlighted and histological features common to Fabry nephropathy and MCD are discussed, along with the challenges associated with the diagnosis and clinical management.

Enzyme Replacement Therapy for Fabry Disease Anderson-Fabry disease (FD) is a X-linked lysosomal storage disorder, which involves glycosphingolipids metabolism. Specific treatment for FD has been available in the last two decades, after the development and commercialization of recombinant human alfa-galactosidase A. Since then enzyme replacement therapy (ERT) has changed the natural history of the disease. Two different enzymatic formulations are available: agalsidase alfa and agalsidase beta at different dosages. The safety and efficacy profiles are similar. ERT induces Gb3 deposits reduction in renal and cardiac biopsies, improves quality of life, reduces pain and GI symptoms, decreases left ventricular mass and slows down renal function decline. In case of organ involvement, clinical evidence confirms the need to treat all patients with enzyme therapy, both male and female. In all other clinical settings, the decision to start ERT is controversial, because of the extremely variable clinical manifestations of FD. However, data suggest a greater response to ERT if started as early as possible in any patients. Timely treatment appears to be effective in stabilizing and possibly delaying FD progression. ERT infusion reactions due to allergic hypersensitivity or IgG antibody development could occur but can be easily managed. In-hospital and at home infusions are possible. The wide genetic and phenotypic heterogeneity observed in all FD patients requires a tailored approach to treatment options. Patients should be referred to an expert multidisciplinary team for the long term management of this challenging disease.