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BACKGROUND: Cardiovascular disease is the most common cause of death among Fabry disease patients, who carry significantly increased risk for heart failure and sudden cardiac death. Echocardiographic strain imaging and cardiac MRI are important clinical tools for early detection of cardiomyopathy before onset of systolic or diastolic dysfunction. However, studies on these imaging modalities are limited among Fabry patients. AIM AND OBJECTIVE: To evaluate echocardiographic strain pattern and correlation with cardiac MRI in Fabry disease. MATERIALS AND METHODS: We performed a detailed analysis of global longitudinal strain and correlation with cardiac MRI finding in 9 patients diagnosed with Fabry disease. RESULTS: Despite normal left ventricular ejection fraction, basal and mid inferior segments are more likely to demonstrate strain abnormalities compared to other regions. Additionally, increased interventricular septal and left ventricular posterior wall thickness are correlated with greater strain abnormalities. Finally, MRI evidence of fibrosis and infiltration are detected among most patients with strain abnormalities, but in some cases, strain imaging were able to detect early evidence of cardiomyopathy even before MRI was fully able to detect the change. Basal and mid inferoseptal segment strain abnormalities are early signs of developing cardiomyopathy among patients with Fabry disease. CONCLUSION: Though cardiac MRIs are critical tools for detection of myocardial infiltration and scarring, these findings may not always be detectable in early phases of the disease. Multiple imaging modalities maybe considered in monitoring and evaluation of cardiomyopathy in Fabry disease.
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OBJECTIVE: To characterize the prevalence of brain ischemia and cerebral small vessel disease in a cohort of patients with Fabry disease (FD) seen at an academic medical center. BACKGROUND: FD is an inherited X-linked lysosomal storage disorder with central nervous system involvement. Limited data are available in the literature on the cerebrovascular neuroimaging findings in FD, and the reported prevalence of stroke symptoms and cerebral small vessel disease has varied widely. DESIGN/METHODS: Brain MRI was performed in 21 patients with FD followed at University of California Irvine Medical Center. Stroke symptoms were assessed and quantification of cerebral microvascular disease was performed using small vessel disease (SVD) score. Lacunes and deep white matter hyperintensities were scored on a four-point scale of 0 (absent) and 1-3 to account for increasing severity; microbleeds were scored 0 (absent) or 1 (present). The total SVD score is the sum of the three components and ranges from 0 to 7. RESULTS: Nearly 43% (9/21) of our FD cohort (aged 32-81 years, mean = 50) had a SVD score of one or higher, all of whom were aged 50 or more years. The most common MRI-defined SVD was white matter hyperintensities (9/9, 100%), followed by microbleeds (6/9, 66%), and lacunes (3/9, 33%). The three patients with previous strokes had some of the highest SVD scores reported in the cohort (scores 3-5). CONCLUSIONS: In this cohort, the prevalence of SVD (43%) was three times higher than prevalence of stroke symptoms. SVD score was highest in the those who had experienced a stroke. These findings emphasize the importance of routine MRI screening of patients with FD in order to identify and treat high risk patients.
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Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme α-galactosidase A due to mutations in the GLA gene. This leads to an accumulation of globotriaosylceramide (GL-3) in many tissues, which results in progressive damage to the kidneys, heart, and nervous system. We present the molecular and clinical characteristics and long-term outcomes of FD patients from a multidisciplinary clinic at the University of California, Irvine treated with agalsidase beta enzyme replacement therapy (ERT) for 2-20 years. This cohort comprised 24 adults (11 males, 13 females) and two male children (median age 45; range 10-68 years). Of the 26 patients in this cohort, 20 were on ERT (12 males, 8 females). We describe one novel variant not previously reported in the literature in a patient with features of 'classic' FD. The vast majority of patients in this cohort presented with symptoms of 'classic' FD including peripheral neuropathic pain, some form of cardiac involvement, angiokeratomas, corneal verticillata, hypohidrosis, tinnitus, and gastrointestinal symptoms, primarily abdominal pain. The majority of males had clinically evident renal involvement. An annual eGFR reduction of -1.88 mL/min/1.73 m2/yr during the course of ERT was seen in this cohort. The most common renal presentation was proteinuria, and one individual required a renal transplant. Other common findings were pulmonary involvement, lymphedema, hearing loss, and significantly, three patients had strokes. Notably, there was a high prevalence of endocrine dysfunction and low bone mineral density, including several with osteoporosis. While enzyme replacement therapy (ERT) cleared plasma GL-3 in this cohort, there was limited improvement in renal function or health-related quality of life based on the patient-reported SF-36 Health Survey. Physical functioning significantly declined over the course of ERT treatment, which may be, in part, due to the late initiation of ERT in several patients. Further delineation of the phenotypic and genotypic spectrum in patients with FD and the long-term outcome of ERT will help improve management and treatment options for this disease.
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Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene leading to a deficiency of the enzyme alpha-galactosidase A (α-Gal A). Multiple organ systems are implicated in Fabry disease, most severely the cardiac, kidney, and central nervous systems. In this brief review, we will focus on the kidney and central nervous system involvement.
