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Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical.

Objective: Using a semiautomated volumetric MRI assessment method, we aimed to identify determinants of white matter hyperintensity (WMH) burden in patients with Fabry disease (FD). Methods: Patients with confirmed FD and brain MRI available for this analysis were eligible for this protocol after written consent. Clinical characteristics were abstracted from medical records. T2 fluid-attenuated inversion recovery MRI were transferred in electronic format and analyzed for WMH volume (WMHV) using a validated, computer-assisted method. WMHV was normalized for head size (nWMHV) and natural log-transformed (lnWMHV) for univariate and multivariate linear regression analyses. Level of significance was set at p Results: Of 223 patients with FD and WMHV analyzed, 132 (59%) were female. Mean age at MRI was 39.2 ± 14.9 (range 9.6–72.7) years, and 136 (61%) patients received enzyme replacement therapy prior to enrollment. Median nWMHV was 2.7 cm 3 (interquartile range 1.8–4.0). Age (β 0.02, p = 0.008) and history of stroke (β 1.13, p = 0.02) were independently associated with lnWMHV. However, WMH burden—as well as WMHV predictors—varied by decade of life in this cohort of patients with FD ( p Conclusions: In this largest-to-date cohort of patients with FD who had volumetric analysis of MRI, age and prior stroke independently predicted the burden of WMH. The 4th decade of life appears to be critical in progression of WMH burden, as novel predictors of WMHV emerged in patients aged 31–40 years. Future studies to elucidate the biology of WMH in FD and its role as potential MRI marker of disease progression are needed.

Background Fabry disease is an X-linked lysosomal storage disorder that causes progressive complications within the kidneys, brain, and heart. Ocular manifestations of this disease are often present at a very young age, thereby facilitating early diagnosis, before the signs and symptoms of renal disease, stroke, or hypertrophic cardiomyopathy. Early diagnosis by the eye care provider may eventually reduce the morbidity and mortality of this disease through the institution of therapy before the development of sclerotic end organ damage. This study evaluated 23 Fabry-affected members of a single cohort for the presence of ocular signs of Fabry disease. Methods Twenty-three patients of a single family were seen on a single day. Patients were given comprehensive ophthalmic examinations and completed a health and lifestyle questionnaire. Results Eight hemizygous men (mean age, 32.3 years) and 15 heterozygous women (mean age, 26.9 years) from a single family of 43 known Fabry patients were evaluated. Corneal verticillata was present in all patients. Additional findings in the male patients included anterior capsule opacity (25% total) and Fabry cataract (12.5%). Thinning of the retinal nerve fiber layer was observed in one man whose medical history was significant for stroke. Conjunctival and/or retinal vessel tortuosity was present in the majority of patients (62.5% and 75% of hemizygotes, respectively; 40% and 13.3% heterozygotes, respectively). Additional findings in the women included anterior capsule opacity. The majority of patients (87.5% hemizygotes, 60% heterozygotes) felt Fabry disease had an impact on their quality of life. Conclusions All evaluated patients who had Fabry disease had corneal verticillata, which generally does not affect vision and is readily recognizable by slit lamp examination. Greater than 60% showed conjunctival and/or retinal vessel tortuosity. The eye care provider can play a crucial role in the early recognition of ocular manifestations of Fabry disease and decrease both the time to accurate diagnosis and the delay in the institution of disease-modifying therapy.

We examined the feasibility of recruiting US adults ≥45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case–control design matched each FD participant on age, sex, race, and education to four participants from a population-based study. Fifty-four participants with FD age 46–72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values

Identification and comprehensive care of individuals who have Fabry disease (FD) requires a multidisciplinary approach inclusive of genetic testing, test interpretation, genetic counseling, long term disease symptom monitoring, treatment recommendations, and coordination of therapy. The purpose of this document is to provide health care professionals with guidelines for testing, care coordination, identification of psychosocial issues, and to facilitate a better understanding of disease treatment expert recommendations for patients with Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as representatives/founders of the two United States based Fabry disease patient advocacy groups who are themselves affected by Fabry disease. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing, interpretation of results, psychosocial considerations, and references to professional and patient resources.