Background: Fabry disease (FD) is a X-linked recessive lysosomal storage disorder characterized by altered biodegradation of glycosphingolipids. It is a multisystem pathology, also involving ophthalmological systems that show modifications of the vessel wall due to glycosphingolipid deposits. Optical coherence tomography angiography (OCT-A) allows for an objective analysis of retinal microvasculature alterations, evaluating retinal vessel density in macular region. Methods: A total of 54 FD patients (34 females, 20 males, mean age 44.1 ± 15.6 years) and 70 controls (36 females, 34 males, mean age 42.3 ± 15.6 years) were included in this study. We evaluated vessel density in different macular areas (whole image, fovea, and parafovea) of both the superficial capillary plexus (SCP) and of the deep capillary plexus (DCP). Results: In the SCP there was a significantly lower vascular density in patients compared with controls in whole image (49.95 ± 5.17% vs. 51.99 ± 2.52%; p < 0.001), parafovea (52.01 ± 6.69% vs. 54.30 ± 2.61%; p = 0.002), and fovea (22.38 ± 9.01% vs. 29.31 ± 5.84%; p < 0.0001). In the DCP the vessel density was statistically increased in each macular area in patients compared with controls (54.82 ± 8.07% vs. 50.93 ± 5.46%; p = 0.005, 57.76 ± 7.26% vs. 53.59 ± 5.46%; p = 0.0001, and 39.75 ± 8.59% vs. 34.43 ± 8.68%; p < 0.0001 for whole image, parafovea, and fovea, respectively). Conclusion: OCT-A analysis showed that the macular vessel density was significantly reduced in the SCP and increased in the DCP in FD patients compared with controls. These findings, which might be a consequence of the alteration of vascular wall occurring in FD, support the hypothesis that the evaluation of early retinal microvascular network changes could be a useful tool in the clinical evaluation of the disease.

Background Speckle tracking advancements make now available the analysis of layer‐specific myocardial deformation. This study investigated multilayer longitudinal strain in Anderson–Fabry disease (AFD) patients at diagnosis. Methods In a case–control study, 33 newly diagnosed, untreated AFD patients and 33 healthy age‐ and sex‐matched healthy controls underwent a complete echocardiogram, including assessment of left ventricular (LV) transmural global longitudinal strain (GLS), subendocardial longitudinal strain (LSsubendo), subepicardial longitudinal strain (LSsubepi), and strain gradient (LSsubendo–LSsubpepi). Results Anderson–Fabry disease patients had similar blood pressure, heart rate, and ejection fraction but higher body mass index in comparison with controls. LV mass index, maximal, and relative wall thickness were significantly greater in AFD patients. LSsubendo was significantly higher than LSsubepi in both groups, but GLS (P < 0.0001), LSsubendo (P = 0.003), and particularly LSsubepi (21.4 ± 1.7 vs 18.8 ± 1.4%, P < 0.0001) were lower in AFD patients than in controls. Accordingly, LS gradient was higher in AFD patients (P = 0.003). Three patients symptomatic for dyspnoea presented a combination of LV hypertrophy and reduced LSsubepi. After adjusting for confounders by multivariate analyses, LV mass index or maximal wall thickness were independently and inversely associated with transmural GLS and LSsubepi, but not with LSsubendo in the AFD group. At receiver operating curve curves, LSsubepi best discriminated AFD and normals. Conclusions In newly diagnosed, untreated AFD patients, layer‐specific strain imaging highlights an impairment of LV longitudinal deformation, mainly involving subepicardial strain and causing increase in longitudinal strain myocardial gradient. These findings could be useful for identifying the mechanisms underlying early LV dysfunction in AFD patients.

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Background Fabry disease (FD) is a rare X-linked disease caused by mutations in GLA gene with consequent lysosomal accumulation of globotriaosylceramide (Gb3). Women with FD often show highly heterogeneous symptoms that can manifest from mild to severe phenotype. Main body The phenotypic variability of the clinical manifestations in heterozygous women with FD mainly depends on the degree and direction of inactivation of the X chromosome. Classical approaches to measure XCI skewness might be not sufficient to explain disease manifestation in women. In addition to unbalanced XCI, allele-specific DNA methylation at promoter of GLA gene may influence the expression levels of the mutated allele, thus impacting the onset and the outcome of FD. In this regard, analyses of DNA methylation at GLA promoter, performed by approaches allowing distinction between mutated and non-mutated allele, may be much more informative. The aim of this review is to critically evaluate recent literature articles addressing the potential role of DNA methylation in the context of FD. Although up to date relatively few works have addressed this point, reviewing all pertinent studies may help to evaluate the importance of DNA methylation analysis in FD and to develop new research and technologies aimed to predict whether the carrier females will develop symptoms. Conclusions Relatively few studies have addressed the complexity of DNA methylation landscape in FD that remains poorly investigated. The hope for the future is that ad hoc and ultradeep methylation analyses of GLA gene will provide epigenetic signatures able to predict whether pre-symptomatic female carriers will develop symptoms thus helping timely interventions.