15 research outputs found
Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.
BackgroundThe p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease.MethodsTo expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events.ResultsIn p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%).Conclusionp.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males
Fabry disease and COVID-19: International expert recommendations for management based on real-world experience
The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin–angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established
Attention Deficits and ADHD Symptoms in Adults with Fabry Disease—A Pilot Investigation
The present pilot study examines subjective reported symptoms of attention-deficit/hyperactivity (AD/H) in adults with Fabry disease (FD) in comparison with existing normative control data. Existing data from 69 adults with FD via the Achenbach System of Empirically Based Assessment Adult Self-Report questionnaire were analyzed. The results demonstrated a higher prevalence of AD/H symptoms in adults with FD than in the general United States population, with a roughly equal endorsement of Inattention/Attention Deficit symptoms (AD), Hyperactivity-Impulsivity (H-I) symptoms, and Combined Inattention/hyperactivity-impulsivity (C) symptoms. No gender differences were observed. While all subjects endorsing H-I symptoms fell into the symptomatic range on the AD/H scale, only two-thirds of subjects endorsing AD did so. This suggests that attention difficulties with FD are not solely explained by ADHD. Adults with FD who endorsed the AD, H-I, and C symptoms were also more likely to report mean adaptive functioning difficulties. These findings support the growing literature regarding attention difficulties in adults with FD, as well as suggesting a previously unrecognized risk of AD/H symptoms. Future research involving the objective assessment of ADHD in adults with FD is recommended. When serving adults with FD clinically, healthcare professionals should address multiple areas of care, including physical, psychological, and cognitive arenas
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Validation of a suspicion index to identify patients at risk for hereditary angioedema.
BACKGROUND: Hereditary angioedema (HAE) is a genetic condition characterized by dysregulation of the contact (kallikrein-bradykinin) pathway, leading to recurrent episodes of angioedema. OBJECTIVE: This project sought to determine whether a suspicion index screening tool using electronic health record (EHR) data can identify patients with an increased likelihood of a diagnosis of HAE. METHODS: A suspicion index screening tool for HAE was created and validated by using known patients with HAE from the medical literature as well as positive and negative controls from HAE-focused centers. Through the use of key features of medical and family history, a series of logistic regression models for 5 known genetic causes of HAE were created. Top variables populated the digital suspicion scoring system and were run against deidentified EHR data. Patients at 2 diverse sites were categorized as being at increased, possible, or no increased risk of HAE. RESULTS: Prediction scoring using the strongest 13 variables on the real-world EHR-positive control data identified all but 1 patient with C1 inhibitor deficiency and patient with non-C1 inhibitor deficiency without false-positive results. The 2 missed patients had no documented family history of HAE in their EHR. When the prediction scoring variables were expanded to 25, the screening algorithm approached 100% sensitivity and specificity. The 25-variable algorithm run on general population EHR data identified 26 patients at the medical centers as being at increased risk for HAE. CONCLUSIONS: These results suggest that development, validation, and implementation of suspicion index screening tools can be useful to aid providers in identifying patients with rare genetic conditions