Patient-reported experience with Fabry disease and its management in the real-world setting: results from a double-blind, cross-sectional survey of 280 respondents.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a heterogeneous clinical presentation. Patients with FD may exhibit early signs/symptoms including neuropathic pain, gastrointestinal complaints, and dermatologic manifestations. FD may ultimately progress to renal, neurologic, and cardiac dysfunction. Current treatments for FD have significantly improved the management and outcomes for patients with FD, but important clinical and convenience limitations still exist. METHODS: To illuminate the impact of FD on daily life from the patient's perspective, we asked adult patients (≥ 18 years old) with FD in the United States and Canada to complete a 33-question online survey to assess patient-reported disease severity, management, and treatment outcomes. RESULTS: A total of 280 respondents with FD completed the survey; they had a mean age of 47 years, and 68% (191/280) were women. Most were currently receiving FD treatment (84%, 234/280) with enzyme replacement therapy (ERT) (89%, 208/234) or chaperone therapy (11%, 26/234). Common symptoms included low energy/fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands/feet (60%, 168/280), ringing in ears/hearing loss (54%, 151/280), general body pains/pain crises (51%, 143/280), and abdominal/stomach pain (50%, 140/280). More than half (51%, 144/280) of respondents reported their symptoms as bothersome (38%, 106/280) or difficult to control (14%, 38/280). Temporary symptom worsening between infusions was reported by about half of respondents: 51% (108/211) currently receiving ERT and 48% (14/29) previously receiving ERT. Only 48% (59/122) of respondents reported their symptom worsening to their physician. Of those who reported it, 41% (24/59) said that their physician prescribed medication to manage their symptoms or changed their treatment regimen. CONCLUSIONS: Our analysis highlights the gap between current standard-of-care in disease monitoring and patient perception of disease progression among patients with FD. This information may be helpful for healthcare providers and drug developers seeking to improve the care of patients with FD by addressing unmet needs of high relevance.

Insights from the 2-year-long human confinement experiment in Grand Cayman reveal the resilience of coral reef fish communities.

In March 2020, the world went into lockdown to curb the spread of the novel coronavirus (SARS-CoV-2), with immediate impacts on wildlife across ecosystems. The strict 2-year long lockdown in Grand Cayman provided an unprecedented opportunity to assess how the 'human confinement experiment' influenced the community composition of reef fish. Using a suite of multivariate statistics, our findings revealed a stark increase in reef fish biomass during the 2 years of lockdown, especially among herbivores, including parrotfish, with drastic increases in juvenile parrotfishes identified. Additionally, when comparing baseline data of the community from 2018 to the 2 years during lockdown, over a three-fold significant increase in mean reef fish biomass was observed, with a clear shift in community composition. Our findings provide unique insights into the resilience of reef fish communities when local anthropogenic stressors are removed for an unprecedented length of time. Given the functional role of herbivores including parrotfish, our results suggest that reductions in human water-based activities have positive implications for coral reef ecosystems and should be considered in future management strategies.

Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community.

Fabry disease (FD, α-galactosidase A deficiency) is a rare, progressive, complex lysosomal storage disorder affecting multiple organ systems with a diverse spectrum of clinical phenotypes, particularly among female patients. Knowledge of its clinical course was still limited in 2001 when FD-specific therapies first became available and the Fabry Registry (NCT00196742; sponsor: Sanofi) was initiated as a global observational study. The Fabry Registry has now been operational for over 20 years, overseen by expert Boards of Advisors, and has collected real-world demographic and longitudinal clinical data from more than 8000 individuals with FD. Leveraging the accumulating evidence base, multidisciplinary collaborations have resulted in the creation of 32 peer-reviewed scientific publications, which have contributed to the greatly expanded knowledge on the onset and progression of FD, its clinical management, the role of sex and genetics, the outcomes of enzyme replacement therapy with agalsidase beta, and prognostic factors. We review how the Fabry Registry has evolved from its inception to become the largest global source of real-world FD patient data, and how the generated scientific evidence has helped to better inform the medical community, individuals living with FD, patient organizations, and other stakeholders. The patient-centered Fabry Registry fosters collaborative research partnerships with the overarching goal of optimizing the clinical management of patients with FD and is well positioned to add to its past achievements.

Resilient amphipods: Gammarid predatory behaviour is unaffected by microplastic exposure and deoxygenation.

Microplastics are a ubiquitous and persistent form of pollution globally, with impacts cascading from the cellular to ecosystem level. However, there is a paucity in understanding interactions between microplastic pollution with other environmental stressors, and how these could affect ecological functions and services. Freshwater ecosystems are subject to microplastic input from anthropogenic activities (eg. wastewater), but are also simultaneously exposed to many other stressors, particularly reduced dissolved oxygen availability associated with climatic warming and pollutants, as well as biological invasions. Here, we employ the comparative functional response method (CFR; quantifying and comparing organism resource use as a function of resource density) to investigate the relative impact of different microplastic concentrations and oxygen regimes on predatory trophic interactions of a native and an invasive alien gammarid (Gammarus duebeni and Gammarus pulex). No significant effect on trophic interaction strengths was found from very high concentrations of microplastics (200 mp/L and 200,000 mp/L) or low oxygen (40 %) stressors on either species. Additionally, both gammarid species exhibited significant Type II functional responses, with attack rates and handling times not significantly affected by microplastics, oxygen or gammarid invasion status. Thus, both species showed resistance to the simultaneous effects of microplastics and deoxygenation in terms of feeding behaviour. Based on these findings, we suggest that the trophic function, in terms of predation rate, of Gammarus spp. may be sustained under acute bouts of microplastic pollution even in poorly­oxygenated waters. This is the first study to investigate microplastic and deoxygenation interactions and to find no evidence for an interaction on a key invertebrate ecosystem service. We argue that our CFR methods can help understand and predict the future ecological ramifications of microplastics and other stressors across taxa and habitats.

Role of Methanesulfonic Acid in Sulfuric Acid-Amine and Ammonia New Particle Formation.

Aerosol nucleation accounts for over half of all seed particles for cloud droplet formation. In the atmosphere, sulfuric acid (SA) nucleates with ammonia, amines, oxidized organics, and many more compounds to form particles. Studies have also shown that methanesulfonic acid (MSA) nucleates independently with amines and ammonia. MSA and SA are produced simultaneously via dimethyl sulfide oxidation in the marine atmosphere. However, limited knowledge exists on how MSA and SA nucleate together in the presence of various atmospherically relevant base compounds, which is critical to predicting marine nucleation rates accurately. This work provides experimental evidence that SA and MSA react to form particles with amines and that the SA-MSA-base nucleation has different reaction pathways than SA-base nucleation. Specifically, the formation of the SA-MSA heterodimer creates more energetically favorable pathways for SA-MSA-methylamine nucleation and an enhancement of nucleation rates. However, SA-trimethylamine nucleation is suppressed by MSA, likely due to the steric hindrance of the MSA and trimethylamine. These results display the importance of including nucleation reactions between SA, MSA, and various amines to predict particle nucleation rates in the marine atmosphere.

Career-Best Changes in Body Mass and Physical Fitness Test Performance Among Division 1 College Football Players Encompassing 28 Years at the Same Institution.

ABSTRACT: Baur, DA, Johnson, JB, Giron-Molina, LG, Caterisano, M, Shaner, C, Caterisano, A, and Gentry, M. Career-best changes in body mass and physical fitness test performance among Division 1 college football players encompassing 28 years at the same institution. J Strength Cond Res 37(4): 806-815, 2023-Understanding typical changes induced by collegiate American football strength and conditioning programs is essential for optimizing program design and athletic development. The purpose of the study was to evaluate body mass and physical fitness test performance changes at a Division 1 program with 28 years of coaching stability. Initial and personal record results were collected from 1,102 players who were subdivided into 3 position groups: combination players (COMBO), skill players (SKILL), and line of scrimmage players. Players followed a linear periodized training program with biannual body mass and performance testing. Tested variables included body mass, strength (bench press, back squat, and front squat), impulse (power clean, push jerk, and vertical jump [VJ]), and speed/agility (10-yard dash [10YD], 40-yard dash, and 20-yard shuttle). The fixed effect of time and position group on the dependent variables was assessed using linear mixed models. If appropriate, post hoc tests using the estimated marginal means were used to evaluate the source of any significant effects. Significance was accepted as p < 0.05. Normative values were produced by descriptive statistics (i.e., weighted means). All players and position groups increased/improved across all tested variables ( p < 0.05). Improvements were 8.2%, 11.9-18.3%, 13.5-17.5%, and 3.6-6.0% for body mass, strength, impulse, and speed/agility, respectively. Line of scrimmage improvements were absolutely larger across most tested variables and relatively larger for back squat, VJ, and 10YD vs. SKILL and with VJ vs. COMBO/SKILL ( p < 0.05). These results reveal typical expectations for 4-5 years performance improvements and that position group differences in trainability may influence game readiness and training needs.

Ion-Molecule Rate Constants for Reactions of Sulfuric Acid with Acetate and Nitrate Ions.

Atmospheric nucleation from precursor gases is a significant source of cloud condensation nuclei in the troposphere and thus can affect the Earth's radiative balance. Sulfuric acid, ammonia, and amines have been identified as key nucleation precursors in the atmosphere. Studies have also shown that atmospheric ions can react with sulfuric acid to form stable clusters in a process referred to as ion-induced nucleation (IIN). IIN follows similar reaction pathways as chemical ionization, which is used to detect and measure nucleation precursors via atmospheric pressure chemical ionization mass spectrometers. The rate at which ions form clusters depends on the ion-molecule rate constant. However, the rate constant varies based on the ion composition, which is often not known in the atmosphere. Previous studies have examined ion-molecule rate constants for sulfuric acid and nitrate ions but not for other atmospherically relevant ions like acetate. We report the relative rate constants of ion-molecule reactions between nitrate and acetate ions reacting with sulfuric acid. The ion-molecule rate constant for acetate and sulfuric acid is estimated to be a factor of 1.9-2.4 times higher than that of the known rate constant for nitrate and sulfuric acid. Using quantum chemistry, we find that acetate has a higher dipole moment and polarizability than nitrate. This may contribute to an increase in the collision cross-sectional area between acetate and sulfuric acid and lead to a greater reaction rate constant than nitrate. The ion-molecule rate constant for acetate with sulfuric acid will help quantify the contribution of acetate ions to atmospheric ion-induced new particle formation.

Preventing spread of aerosolized infectious particles during medical procedures: A lab-based analysis of an inexpensive plastic enclosure.

Severe viral respiratory diseases, such as SARS-CoV-2, are transmitted through aerosol particles produced by coughing, talking, and breathing. Medical procedures including tracheal intubation, extubation, dental work, and any procedure involving close contact with a patient's airways can increase exposure to infectious aerosol particles. This presents a significant risk for viral exposure of nearby healthcare workers during and following patient care. Previous studies have examined the effectiveness of plastic enclosures for trapping aerosol particles and protecting health-care workers. However, many of these enclosures are expensive or are burdensome for healthcare workers to work with. In this study, a low-cost plastic enclosure was designed to reduce aerosol spread and viral transmission during medical procedures, while also alleviating issues found in the design and use of other medical enclosures to contain aerosols. This enclosure is fabricated from clear polycarbonate for maximum visibility. A large single-side cutout provides health care providers with ease of access to the patient with a separate cutout for equipment access. A survey of medical providers in a local hospital network demonstrated their approval of the enclosure's ease of use and design. The enclosure with appropriate plastic covers reduced total escaped particle number concentrations (diameter > 0.01 µm) by over 93% at 8 cm away from all openings. Concentration decay experiments indicated that the enclosure without active suction should be left on the patient for 15-20 minutes following a tracheal manipulation to allow sufficient time for >90% of aerosol particles to settle upon interior surfaces. This decreases to 5 minutes when 30 LPM suction is applied. This enclosure is an inexpensive, easily implemented additional layer of protection that can be used to help contain infectious or otherwise potentially hazardous aerosol particles while providing access into the enclosure.

The relative influence of sea surface temperature anomalies on the benthic composition of an Indo-Pacific and Caribbean coral reef over the last decade.

Rising ocean temperatures are the primary driver of coral reef declines throughout the tropics. Such declines include reductions in coral cover that facilitate the monopolization of the benthos by other taxa such as macroalgae, resulting in reduced habitat complexity and biodiversity. Long-term monitoring projects present rare opportunities to assess how sea surface temperature anomalies (SSTAs) influence changes in the benthic composition of coral reefs across distinct locations. Here, using extensively monitored coral reef sites from Honduras (in the Caribbean Sea), and from the Wakatobi National Park located in the center of the coral triangle of Indonesia, we assess the impact of global warming on coral reef benthic compositions over the period 2012-2019. Bayesian generalized linear mixed effect models revealed increases in the sponge, and hard coral coverage through time, while rubble coverage decreased at the Indonesia location. Conversely, the effect of SSTAs did not predict any changes in benthic coverage. At the Honduras location, algae and soft coral coverage increased through time, while hard coral and rock coverage were decreasing. The effects of SSTA at the Honduras location included increased rock coverage, but reduced sponge coverage, indicating disparate responses between both systems under SSTAs. However, redundancy analyses showed intralocation site variability explained the majority of variance in benthic composition over the course of the study period. Our findings show that SSTAs have differentially influenced the benthic composition between the Honduras and the Indonesian coral reefs surveyed in this study. However, the large intralocation variance that explains the benthic composition at both locations indicates that localized processes have a predominant role in explaining benthic composition over the last decade. The sustained monitoring effort is critical for understanding how these reefs will change in their composition as global temperatures continue to rise through the Anthropocene.

Experimental and Theoretical Study on the Enhancement of Alkanolamines on Sulfuric Acid Nucleation.

Alkanolamines such as monoethanolamine (MEA), diethanolamine (DEA), and triethanolamine (TEA) are extensively used for CO2 capture and consumer products. Despite their prevalence in industrial applications, the fate of alkanolamines in the atmosphere remains relatively unknown. One likely reaction pathway for these chemicals in the atmosphere is new particle formation with sulfuric acid. Here, we present the first experimental results showing the formation of sulfuric acid dimers enhanced by MEA, DEA, and TEA from the measurement of molecular clusters. This study examines the nucleation reactions of MEA, DEA, and TEA with sulfuric acid in a clean, laminar flow reactor. The chemical compositions and concentrations of the freshly nucleated clusters were analyzed using a custom-built atmospheric pressure chemical ionization long time-of-flight mass spectrometer known as the Pittsburgh Cluster CIMS. Quantum chemical calculations and kinetic modeling of sulfuric acid-MEA/DEA/TEA clusters were also performed to determine relative cluster stabilities between these sulfuric acid-base systems. Experimental results indicate that MEA, DEA, and TEA at the part per trillion by volume (pptv) concentrations can enhance sulfuric acid dimer formation rates but to a lesser extent than dimethylamine (DMA). Thus, MEA, DEA, and TEA will potentially play an important role in new particle formation in industrial cities where these alkanolamines are emitted.

Marine protected areas do not buffer corals from bleaching under global warming.

BACKGROUND: The rising temperature of the oceans has been identified as the primary driver of mass coral reef declines via coral bleaching (expulsion of photosynthetic endosymbionts). Marine protected areas (MPAs) have been implemented throughout the oceans with the aim of mitigating the impact of local stressors, enhancing fish biomass, and sustaining biodiversity overall. In coral reef regions specifically, protection from local stressors and the enhanced ecosystem function contributed by MPAs are expected to increase coral resistance to global-scale stressors such as marine heatwaves. However, MPAs still suffer from limitations in design, or fail to be adequately enforced, potentially reducing their intended efficacy. Here, we address the hypothesis that the local-scale benefits resulting from MPAs moderate coral bleaching under global warming related stress. RESULTS: Bayesian analyses reveal that bleaching is expected to occur in both larger and older MPAs when corals are under thermal stress from marine heatwaves (quantified as Degree Heating Weeks, DHW), but this is partially moderated in comparison to the effects of DHW alone. Further analyses failed to identify differences in bleaching prevalence in MPAs relative to non-MPAs for coral reefs experiencing different levels of thermal stress. Finally, no difference in temperatures where bleaching occurs between MPA and non-MPA sites was found. CONCLUSIONS: Our findings suggest that bleaching is likely to occur under global warming regardless of protected status. Thus, while protected areas have key roles for maintaining ecosystem function and local livelihoods, combatting the source of global warming remains the best way to prevent the decline of coral reefs via coral bleaching.

Genetic Variants in Host Protein Disulfide Isomerase 2 (PDIA2) are Associated with Susceptibility to Chlamydia Trachomatis Infection.

OBJECTIVES: Objective: Host genetics can influence susceptibility to Chlamydia trachomatis infection. This study examined two genetic variants in human protein disulfide isomerase A2 (PDIA2), a member of a family of protein chaperones that participate in the chlamydial life cycle. Methods: A total of 278 male and female subjects, positive or negative for C. trachomatis infection, were genotyped for PDIA2 polymorphisms (rs400037 and rs419949) using real-time PCR and pyrosequencing. Results: There was a significant odds ratio of 8.21 (95% CI: 1.77-38.16) for rs400037 and 9.89 (95% CI: 1.19-82.10) for rs419949, for the AA genotypes. Conclusion: This indicates that individuals with the PDIA2 AA genotypes have significantly increased susceptibility to C. trachomatis infection as compared to the other PDIA2 genotypes (GG, GA). This correlation may be explained by an interactive role of host protein disulfide isomerases in the attachment and entry of C. trachomatis into cells.

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

OBJECTIVES: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. DESIGN AND SETTING: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. RESULTS: A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. CONCLUSIONS: PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.

Drone and Other Hobbyist Aircraft Injuries Seen in U.S. Emergency Departments, 2010-2017.

INTRODUCTION: Recreational radio-controlled hobbyist aircraft-particularly "drones"-have become increasingly popular in the last decade. The purpose of this study is to describe injuries associated with hobbyist drones and compare them with injuries associated with other hobbyist aircraft. METHODS: In this 2018 cross-sectional analysis of National Electronic Injury Surveillance System data for 2010-2017, case narrative fields were searched to identify emergency department visits related to hobbyist aircraft injuries. The incidence of hobbyist aircraft injuries was estimated, and summary statistics, chi-square tests, and t-tests were used to describe and compare the demographic and clinical characteristics of drone and other hobbyist aircraft-related cases. RESULTS: An estimated 12,842 hobbyist aircraft injuries presented to U.S. emergency departments during 2010-2017. An increased incidence attributable to drone-related injuries emerged in 2015. Overall, most injuries involved male patients aged 50 years on average. Propeller injuries were the leading mechanism. An estimated 270 patients required hospital admission. Patients injured by drones were younger (mean, 34 years vs 58 years; p<0.001) and more likely to be female than patients injured by hobbyist planes. Drone-related injuries were more likely than plane-related injuries to result from blunt trauma (e.g., being struck or falling during aircraft retrieval; 40.5% vs 7.9%, p<0.001). Helicopter-related injuries more closely resembled drone-related injuries than plane-related injuries. CONCLUSIONS: Hobbyist aircraft-related injuries are increasing, particularly drone-related injuries. Tailored injury prevention measures and product safety materials are needed to address all hobbyist aircraft-related injuries, with a particular focus on drone-related injury prevention measures.

Symptoms and Quality of Life in Patients with Fabry Disease: Results from an International Patient Survey.

INTRODUCTION: Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A. Symptoms include neuropathic pain and gastrointestinal problems, such as diarrhoea. To inform and support the design of a Phase III clinical trial for a new oral treatment for Fabry disease, this study evaluated patients' experiences of Fabry disease symptoms, the impact of symptoms on their quality of life, and their views on participating in clinical trials. METHODS: An online survey questionnaire was distributed to patients with Fabry disease, through relevant patient organisations. The questionnaire consisted mainly of quantitative, closed questions with pre-defined response options. Fabry-specific pain intensity and its impact on quality of life were rated on a scale from 0 to 10. RESULTS: In total, 367 patients completed the survey, of whom half reported frequent pain, moderate to severe pain, and pain in their hands and feet. Pain frequency, intensity and location were similar for males and females. There was no clear association between Fabry-specific pain and the use of enzyme replacement therapy (ERT), with moderate to severe pain reported by 80.4% of participants receiving ERT and by 75.0% of participants not receiving ERT. Of participants who were receiving ERT, 35.7% said they were willing to discontinue it to take part in a clinical trial testing a new oral drug for treating Fabry disease. Gastrointestinal symptoms were more heterogeneous in nature and frequency than Fabry-specific pain, but still affected a significant proportion of participants. CONCLUSIONS: Both male and female patients with Fabry disease experience significant Fabry-specific pain, which affects their quality of life. Furthermore, frequent diarrhoea affects many patients. The symptoms occur independently of the use of ERT. This suggests the healthcare needs of patients with Fabry disease are not being fully met, and additional treatments are required to improve symptoms and quality of life. FUNDING: This study was sponsored by Actelion Pharmaceuticals Ltd. Study sponsorship was transferred to Idorsia Pharmaceuticals Ltd in July 2018.

Structure and function analysis of the C. elegans aminophospholipid translocase TAT-1.

The Caenorhabditis elegans aminophospholipid translocase TAT-1 maintains phosphatidylserine (PS) asymmetry in the plasma membrane and regulates endocytic transport. Despite these important functions, the structure-function relationship of this protein is poorly understood. Taking advantage of the tat-1 mutations identified by the C. elegans million mutation project, we investigated the effects of 16 single amino acid substitutions on the two functions of the TAT-1 protein. Two substitutions that alter a highly conserved PISL motif in the fourth transmembrane domain and a highly conserved DKTGT phosphorylation motif, respectively, disrupt both functions of TAT-1, leading to a vesicular gut defect and ectopic PS exposure on the cell surface, whereas most other substitutions across the TAT-1 protein, often predicted to be deleterious by bioinformatics programs, do not affect the functions of TAT-1. These results provide in vivo evidence for the importance of the PISL and DKTGT motifs in P4-type ATPases and improve our understanding of the structure-function relationship of TAT-1. Our study also provides an example of how the C. elegans million mutation project helps decipher the structure, functions, and mechanisms of action of important genes.

Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors.

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.