Involvement In Fabry Disease Research Articles

Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping.

Fabry disease (FD) is an X-linked multi-organ disorder of lysosomal metabolism with cardiac disease being the leading cause of death. Identifying early FD-specific pathologies is important in the context of maximum therapeutic benefit in these stages. Therefore, the aim of this study was to investigate the value of quantitative cardiac T1 mapping as a potential disease-specific surrogate. 16 consecutive FD patients (9 female, 7 male; median age: 54 years, IQR 17) and 16 control patients (9 female, 7 male; median age: 52 years, IQR 20) were investigated at 1.5 Tesla. Native T1 mapping was performed using a modified look locker inversion recovery sequence (MOLLI) and native T1 times were measured within the septal myocardium at the midventricular short-axis section. Also functional parameters, left ventricular morphology, presence of late-gadolinium enhancement, cTnI- and Lyso-Gb3-Levels were evaluated. The median native septal T1 time for FD was 889.0 ms and 950.6 ms for controls (p < 0.003). LGE and positive cTnI values (0.26 ± 0.21) were present in 5 FD patients (31.25 %), and left ventricular hypertrophy (LVH) was present in 4 FD patients (25.00 %). The 4 cTnI and 8 Lyso-Gb3 positive FD patients had significantly lower native T1 values (p < 0.05, respectively p < 0.01). Assuming a T1 cut-off value of 900 ms for the identification of increased cardiac lipid deposit, 9 patients with FD (56.25 %) had pathologic values (4 patients cTnI and 8 patients Lyso-Gb3 positive). Moreover, native septal T1 showed a good negative correlation to Lyso-Gb3 (r = - 0.582; p = 0.018). A pathologic cardiac native T1 time obviously reflects cardiac involvement in the scope of FD at tissue level. In the future native T1 mapping as an imaging biomarker might allow identification of early stages of cardiac involvement in FD before morphological changes are obvious. · Native T1 values are significantly decreased in Fabry disease.. · Native T1 shows promising correlation to cardiac and Fabry-specific biomarkers.. · Native T1 mapping might have great potential for early disease detection and therapy monitoring.. · Roller FC, Fuest S, Meyer M et al. Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping. Fortschr Röntgenstr 2019; 191: 932 - 939.

Renal involvement in Fabry disease.

Renal involvement in Fabry disease.

Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy

BackgroundCardiac involvement is common and is the leading cause of mortality in Fabry disease (FD). We explored the association between cardiovascular magnetic resonance (CMR) myocardial strain, T1 mapping, late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) in patients with FD.MethodsIn this prospective study, 38 FD patients (45.0 ± 14.5 years, 37% male) and 8 healthy controls (40.1 ± 13.7 years, 63% male) underwent 3 T CMR including cine balanced steady-state free precession (bSSFP), LGE and modified Look-Locker Inversion recovery (MOLLI) T1 mapping. Global longitudinal (GLS) and circumferential (GCS) strain and base-to-apex longitudinal strain (LS) and circumferential strain (CS) gradients were derived from cine bSSFP images using feature tracking analysis.ResultsAmong FD patients, 8 had LVH (FD LVH+, 21%) and 17 had LGE (FD LGE+, 45%). Nineteen FD patients (50%) had neither LVH nor LGE (FD LVH- LGE-). None of the healthy controls had LVH or LGE. FD patients and healthy controls did not differ significantly with respect to GLS (− 15.3 ± 3.5% vs. − 16.3 ± 1.5%, p = 0.45), GCS (− 19.4 ± 3.0% vs. -19.5 ± 2.9%, p = 0.84) or base-to-apex LS gradient (7.5 ± 3.8% vs. 9.3 ± 3.5%, p = 0.24). FD patients had significantly lower base-to-apex CS gradient (2.1 ± 3.7% vs. 6.5 ± 2.2%, p = 0.002) and native T1 (1170.2 ± 37.5 ms vs. 1239.0 ± 18.0 ms, p < 0.001). Base-to-apex CS gradient differentiated FD LVH- LGE- patients from healthy controls (OR 0.42, 95% CI: 0.20 to 0.86, p = 0.019), even after controlling for native T1 (OR 0.24, 95% CI: 0.06 to 0.99, p = 0.049). In a nested logistic regression model with native T1, model fit was significantly improved by the addition of base-to-apex CS gradient (χ2(df = 1) = 11.04, p < 0.001). Intra- and inter-observer agreement were moderate to good for myocardial strain parameters: GLS (ICC 0.849 and 0.774, respectively), GCS (ICC 0.831 and 0.833, respectively), and base-to-apex CS gradient (ICC 0.737 and 0.613, respectively).ConclusionsCMR reproducibly identifies myocardial strain abnormalities in FD. Loss of base-to-apex CS gradient may be an early marker of cardiac involvement in FD, with independent and incremental value beyond native T1.

Cornea verticillata in Fabry disease.

To study the frequency of cornea verticillata in patients with Fabry disease and it's relation to the severity of the disease and the types of mutation in the GLA gene. We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (&lt;20), moderate (20-40), and severe (&gt;40) clinical categories. At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease.

Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study

BackgroundInitiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes. MethodsThe Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials.gov, NCT01210196) evaluated clinical and diagnostic assessments for early detection of Fabry-related organ pathology in ERT-naïve patients with mild FD symptoms. Assessments included cardiac magnetic resonance imaging with late gadolinium enhancement (LGE-CMR), echocardiography, 24-h Holter electrocardiography, and biomarkers of FD and fibrosis. Results35 patients with mean (SD) baseline age of 45.0 (10.2) years were included and assessed at baseline, 12 months, and (optionally) at 24 months. At baseline, LGE-CMR and elevated procollagen III N-terminal propeptide, sphingosine-1-phosphate, and globotriaosylsphingosine were the most prevalent indicators of early Fabry-related pathology. LGE was already present in 58.8% of patients with normal left ventricular mass index. 15.2% of patients showed grade 1 diastolic dysfunction. QRS duration increased from baseline to last observation, particularly in patients with severe baseline fibrosis. Fibrosis progressed from baseline to last observation, especially in patients with baseline LGE ≥ 2.50 mL (3.65 [1.14] mL vs 6.74 [1.10] mL). Statistically significant correlations were found between LGE volume and high-sensitivity troponin T, and between LGE volume and fragments of urinary collagen alpha-1 (I), (III), and (VII), and collagen alpha-3 (V). ConclusionsFibrosis may become apparent before left ventricular hypertrophy occurs. LGE-CMR imaging is superior to conventional echocardiography for detecting early cardiomyopathy in FD and, in conjunction with biomarker tests, may help detect early organ involvement in mild FD.

Reduced Intracranial Volume in Fabry Disease: Evidence of Abnormal Neurodevelopment?

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition.Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived.Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10−5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures.Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.

Striatonigral involvement in Fabry Disease: A quantitative and volumetric Magnetic Resonance Imaging study

IntroductionAim of this study is to elucidate possible mechanisms of extrapyramidal damage in Fabry Disease (FD), a condition in which involvement of the motor system has been recently suggested, by simultaneously assessing morphometric and susceptibility changes of striatonigral pathway and their possible correlations with clinical variables. MethodsIn this cross-sectional study, we investigated possible differences in terms of Quantitative Susceptibility Mapping (QSM) values and volumes of different extrapyramidal relays, including striatum and substantia nigra (SN), in 30 FD patients (M/F = 11/19, mean age 42.6 ± 12.2) and 37 healthy controls (HC) (M/F = 16/21, mean age 43.2 ± 14.6). Patients underwent a clinical examination for the study of different motor functions, and the relationship between MRI and clinical variables was tested using the Spearman's coefficient. ResultsCompared to HC, FD patients showed an increase in susceptibility values of the SN (p < 0.001) and striatum (p = 0.001), while no difference emerged for the other tested extrapyramidal structures, suggesting their relative sparing. The increased susceptibility was coupled to a reduced volume of the SN (p < 0.001), but not of the striatum (p = 0.34). Finally, no significant correlation emerged when probing the relationship between these modifications and the clinical variables. ConclusionIn FD patients, susceptibility and volumetric alterations are present throughout the extrapyramidal pathway, with the SN being particularly affected by these changes. Such results are in line with the subtle extrapyramidal involvement recently suggested in FD, and could further contribute to the understanding of the physiopathological bases of cerebral involvement in FD.

Variable phenotypic presentations of renal involvement in Fabry disease: a case series

Fabry disease is an X-linked genetic deficiency in the alpha-galactosidase enzyme resulting in intracellular accumulation of glycosphingolipids and multisystem organ dysfunction. Typically 50% of males and 20% of affected females have renal involvement, ranging from proteinuria or reduced renal function, renal parapelvic cysts and progressive renal disease ultimately requiring transplantation or dialysis. The phenotypic presentation of Fabry disease is incredibly varied and will even vary between family members with the same confirmed genetic mutation. In a cohort of patients affected by Fabry disease in the North East of England we examine the different phenotypic presentations of eight index cases (6 male, 2 female) with predominantly renal disease and the renal manifestations within their family members. The mean age of presentation was 40 years of age (range 23-59 years). Various multisystem manifestations were observed including cardiac, neurological, cerebrovascular and skin involvement. Two of the male index patients reached end stage renal disease (ESRD) requiring renal replacement therapy. Two female index patients had phenotypes limited to hypertension and proteinuria at presentation and the remaining patients had either stable or progressive chronic kidney disease at the time of diagnosis. We demonstrate the need for a high index of suspicion in order to consider Fabry disease as a diagnosis and the importance of cascade genetic screening to identify affected family members so that treatment can be initiated in a timely fashion.

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine (Lyso-Gb3) and time to initiation of enzyme replacement therapy, an observational study

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine (Lyso-Gb3) and time to initiation of enzyme replacement therapy, an observational study

Inner ear involvement in Fabry disease: Clinical and audiometric evaluation of a large cohort of patients followed in a reference centre

BackgroundFabry disease (FD) is a lysosomal storage disorder (LSD) that involves the cochleovestibular system. Tinnitus and progressive sensorineural hearing loss are frequent complains. A stabilization of hearing function has been reported with enzyme replacement therapy (ERT). This study aims to characterize the inner ear involvement, identify factors associated to hearing loss and evaluate the effect of ERT on the hearing function of FD patients. MethodsWe reviewed the clinical records of patients with confirmed diagnosis of FD followed in a Reference Centre on LSD in the North of Portugal. ResultsWe included a total of 122 patients with a mean age of 47.1 ± 17.6 years and 48.3% males. Hearing loss was reported by 26.2% of the patients and 23.0% mentioned tinnitus. Pure tone audiometry revealed sensorineural hearing loss in 36.9% of the cases. FD patients presented worse age-adjusted hearing thresholds in all analysed frequencies compared to the normal population (p = .001). Patients with hearing loss presented a significantly higher value of microalbuminuria (p = .001) and a higher frequency of acroparesthesias (p = .032). Patients presented a comparable hearing level one year after starting ERT (p = .384). ConclusionsIn FD, hearing loss is common and age-matched hearing thresholds by frequency are worse than in the general population. Hearing loss was associated to the presence of acroparesthesias and higher values of microalbuminuria. Hearing loss stabilized in patients under ERT. A careful cochleo-vestibular evaluation should be part of the clinical assessment of FD.

Angiographic evidence of small vessel involvement in Fabry disease

Angiographic evidence of small vessel involvement in Fabry disease

Contribution of inflammatory pathways to Fabry disease pathogenesis.

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play a role in many steps of the immune response. Leukocyte perturbation and over-expression of immune molecules have been reported in Fabry disease. Innate immunity is activated by signals originating from dendritic cells via interactions between toll-like receptors and globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate toll-like receptors, thus triggering inflammation and fibrosis cascades. In the kidney, Gb3 deposition is associated with the increased release of transforming growth factor beta and with epithelial-to-mesenchymal cell transition, leading to the over-expression of pro-fibrotic molecules and to renal fibrosis. Interstitial fibrosis is also a typical feature of heart involvement in Fabry disease. Endomyocardial biopsies show infiltration of lymphocytes and macrophages, suggesting a role for inflammation in causing tissue damage. Inflammation is present in all tissues and may be associated with other potentially pathologic processes such as apoptosis, impaired autophagy, and increases in pro-oxidative molecules, which could all contribute synergistically to tissue damage. In Fabry disease, the activation of chronic inflammation over time leads to organ damage. Therefore, enzyme replacement therapy must be started early, before this process becomes irreversible.

Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy: a nationwide Danish cohort study

Objectives: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT. Methods: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring. Results: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0–12] years and 6 [0–13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15–53] vs. 25 mm [3–44], p < 0.005 and 1710 mm·ms [480–3740] vs. 1520 mm·ms [550–5740], p < .05, respectively. There were no changes within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased significantly in the ERT group, whereas no differences were observed within the non-ERT group. Discussion: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research.

New biomarkers defining a novel early stage of Fabry nephropathy: A diagnostic test study.

Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage≥2. In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria<30mg/g; 2) albuminuria 30-299mg/g; 3) albuminuria>300mg/g; 4) glomerular filtration rate (GFR)<60mL/min/1.73m2. Several index tests, namely biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-β-glucosaminidase and alanine aminopeptidase) dysfunction were compared with the reference standard (albuminuria). Significant increase of all tested biomarkers in Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ=-0.289; p=0.003) or N-acetyl-β-glucosaminidase (ρ=-0.448; p<0.001), which were stronger than with albumin (ρ=-0.274; p=0.019). There was also better diagnostic accuracy of N-acetyl-β-glucosaminidase to predict CKD stage≥2. These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage.

Alterations of functional connectivity of the motor cortex in Fabry disease: An RS-fMRI study.

To evaluate the presence of functional connectivity (FC) alterations of the motor circuits in patients with Fabry disease (FD) and their possible correlation with clinical variables with a resting-state (RS) fMRI analysis. In our cross-sectional study, 32 patients with FD with genetically confirmed classic diagnosis of FD (12 men, mean age 43.3 ± 12.2 years) were enrolled along with 35 healthy controls (HCs) of comparable age and sex (14 men, mean age 42.1 ± 14.5 years). RS-fMRI data were analyzed with a seed-based approach, with 2 different seeds for right and left motor cortex. Patients with FD underwent a clinical examination for the assessment of different motor functions. Correlations with clinical variables were probed with the Spearman correlation coefficient. A reduction of FC was found in patients with FD compared to HCs between both motor cortices and 2 clusters encompassing, for each side, the caudate and lenticular nucleus (p < 5 × 10-4 and p < 10-8 for right and left motor cortex, respectively) and between the left motor cortex and dentate nuclei (p = 0.01) and Crus 1 in the right cerebellar hemisphere (p = 0.001). No significant results emerged in tests for possible correlations of FC with clinical scores. An alteration of the corticostriatal pathway is present in FD, in line with the recently suggested subclinical involvement of motor circuits in this disease. These results shed new light on the pattern of cerebral involvement in FD.

Improving the detection of heterozygous females for Fabry disease

Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage ≥ 2.In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria < 30 mg/g; 2) albuminuria 30–299 mg/g; 3) albuminuria > 300 mg/g; 4) glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Several index tests, namely biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-β-glucosaminidase and alanine aminopeptidase) dysfunction were compared with the reference standard (albuminuria).Significant increase of all tested biomarkers in Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ = − 0.289; p = 0.003) or N-acetyl-β-glucosaminidase (ρ = − 0.448; p < 0.001), which were stronger than with albumin (ρ = − 0.274; p = 0.019). There was also better diagnostic accuracy of N-acetyl-β-glucosaminidase to predict CKD stage ≥ 2.These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage.

Cardiac involvement in Fabry disease

Cardiac involvement in Fabry disease

The Central Nervous System Involvement in Fabry Disease

Fabry disease (FD) is an X-linked, lysosomal storage disorder caused by a mutation in the alpha galactosidase (GLA) gene leading to a deficiency in α-galactosidase A enzyme (α-Gal A) activity, whic...

Update on Coronary Involvement in Fabry Disease

Fabry disease is a multisystemic disorder with consequent morbidity and mortality at an early age in patients of both genders. Although renal failure has been previously described as the cause of death with the highest prevalence, recent studies, based on the analysis of the population recorded in the Fabry Registry, reported that 40% of deaths had a cardiovascular origin. Data from the same registry emphasize the high risk for these patients suffering cardiovascular events—particularly acute myocardial infarction—and to the fact that this risk is higher for those patients who need dialysis. Microvascular dysfunction is a constant in patients with Fabry disease, which affects young patients, independently from other cardiac involvement manifestations—such as left ventricular hypertrophy—and from the patient’s gender.