ABSTRACT
BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disorder that might result in, amongst other complications, early stroke and white matter lesions (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease presentation and prognosis in FD. In this systematic review we assessed the prevalence, severity, location and course of WMLs in FD. We also systematically reviewed the evidence on the relation between WMLs, disease characteristics and clinical parameters. METHODS: We searched Pubmed, EMBASE and CINAHL (inception to Feb 2018) and identified articles reporting on FD and WMLs assessed with MRI. Prevalence and severity were assessed for all patients combined and divided by sex. RESULTS: Out of 904 studies a total of 46 studies were included in the analyses. WMLs were present in 46% of patients with FD (581 out of 1276 patients, corrected mean age: 38.8â¯years, range 11.8-79.3) and increased with age. A total of 16.4% of patients (31 out of 189 patients, corrected mean age: 41.1â¯years, range 35.8-43.3â¯years) showed substantial confluent WMLs. Men and women showed comparable prevalence and severity of WMLs. However, men were significantly younger at time of WML assessment. Patients with classical FD had a higher chance on WMLs compared to non-classical patients. Progression of WMLs was seen in 24.6% of patients (49 out of 199 patients) during 38.1â¯months follow-up. Progression was seen in both men and women, with and without enzyme replacement therapy, but at an earlier age in men. Stroke seemed to be related to WMLs, but cerebrovascular risk factors, cardiac and renal (dys)function did not. Pathology in the brain in FD seemed to extend beyond the WMLs into the normal appearing white matter. CONCLUSIONS: A significant group of FD patients has substantial WMLs and male patients develop WMLs earlier compared to female patients. WMLs could be used in clinical trials to evaluate possible treatment effects on the brain. Future studies should focus on longitudinal follow-up using modern imaging techniques, focusing on the clinical consequences of WMLs. In addition, ischemic and non-ischemic pathways resulting in WML development should be studied.
Subject(s)
Fabry Disease/genetics , Stroke/genetics , White Matter/diagnostic imaging , White Muscle Disease/genetics , Adolescent , Adult , Aged , Animals , Child , Disease Progression , Fabry Disease/complications , Fabry Disease/diagnostic imaging , Fabry Disease/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Risk Factors , Stroke/complications , Stroke/diagnostic imaging , Stroke/pathology , White Matter/pathology , White Muscle Disease/complications , White Muscle Disease/diagnostic imaging , White Muscle Disease/pathology , Young AdultABSTRACT
The aim of the present study was to investigate the role of ADAMTS-7 gene in the pathogenesis of myocardial dystrophy associated with white muscle disease (WMD) in lambs. A total of 217 cardiac tissue samples from lambs with WMD were used in the study. Histopathological sections of the samples were stained with hematoxylin-eosin (HE) and examined using Western-blot, real-time PCR (RT-PCR) and immunohistochemistry for ADAMTS-7 gene expression, and the findings were statistically evaluated. Histopathological examinations revealed fibrosis associated with hyalinization, necrosis and granular calcifications in cardiomyocytes. Western blot and RT-PCR showed a statistically significant upregulation of ADAMTS-7 (p<0.05) (p<0.05). Immunohistochemical analyses showed that immunopositive cell numbers significantly high for ADAMTS-7 (p<0.05). The study has revealed that ADAMTS-7 gene is significantly expressed in myocardial dystrophy associated with WMD in addition to its role in the pathogenesis of this disease.
