A comparison of central nervous system involvement in patients with classical Fabry disease or the later-onset subtype with the IVS4+919G&gt;A mutation

Yang

et al. 2018

Euro J of Neurology

Section: Discussionmentioning

confidence: 76%

Genomic screening of Fabry disease in young stroke patients: the Taiwan experience and a review of the literature

Yang

et al. 2018

Euro J of Neurology

“…A recent study on patients with classic and late‐onset Fabry disease, performed by applying a similar MRI protocol, demonstrated a FS > 1 in about 50% of patients studied as well as a recurrence of stroke episodes .…”

Section: Discussionmentioning

confidence: 87%

Central nervous system involvement in late‐onset Pompe disease: clues from neuroimaging and neuropsychological analysis

Musumeci¹,

Marıno

Granata³

et al. 2018

Euro J of Neurology

Background and purpose Late‐onset Pompe disease (LOPD) is a rare, multisystem disorder that is well established to mainly impair skeletal muscle function. Systematic studies exploring brain functions in LOPD are lacking. The aim of this study was to detect morphological and functional brain alterations as well as neuropsychological impairment in LOPD. Methods We studied 21 patients (10 male, mean age 49 ± 18.4 years) with defined diagnosis of LOPD, divided into two groups: one with pre‐symptomatic hyperCKemia with no muscle weakness and the second with limb‐girdle muscle weakness. All patients underwent 3T magnetic resonance imaging (MRI) to obtain morphological/angiographic evaluation as well as normalized cortical brain volume and resting‐state functional MRI. Fazekas score was applied to quantify white matter lesions, whereas Smoker's criteria were used to examine dolichoectasia. A complete neuropsychological assessment was performed. Results The MRI data showed that 12/21 patients (57%) demonstrated signs of cerebral vasculopathy, with a Fazekas score >2 in 67%. According to Smoker's criteria, 11/21 patients (52%) had a dolichoectasia of the vertebrobasilar system; an intracranial aneurysm was detected in 3/21 patients (14%). Resting‐state functional MRI demonstrated significantly decreased brain connectivity in the salience network with a more relevant reduction in the bilateral middle and superior frontal gyrus. Gray matter atrophy correlated with age and disease duration. A mild impairment in executive functions was also identified. Conclusions In this LOPD cohort the results showed morphological and functional brain alterations with mild neuropsychological dysfunction, mainly in the limb‐girdle muscle weakness group. Cerebrovascular alterations seemed to be not related to common risk factors, suggesting a major role of enzymatic deficiency in the pathogenesis of brain abnormalities.

“…However, other extracardiac manifestations, such as proteinuria, brain white matter lesions, and deafness, are common and arise early, before 30 years of age. Their prognostic impact, however, is lower, as renal insufficiency, stroke, and need for a hearing device is uncommon [ 4 , 5 , 150 , 165 , 166 , 169 , 172 , 173 , 174 ].…”

Section: Late-onset Phenotypes With Predominant Cardiac Involvement (“Cardiac Variants”)mentioning

confidence: 99%

Fabry Disease and the Heart: A Comprehensive Review

Azevedo

Cordeiro

Gago

et al. 2021

IJMS

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.