Search Our Scientific Publications & Authors

Neurology 2018 Oct 12;91(15):e1413-e1422. Epub 2018 Sep 12.

From the Greater Manchester Comprehensive Stroke Centre, Clinical Sciences Building (J.D.S., A.R.P.-J., C.J.S.), Department of Neuroradiology, Greater Manchester Neurosciences Centre (G.M.P.), and The Mark Holland Metabolic Unit (A.J.), Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford; and Neuroscience and Aphasia Research Unit, Division of Neuroscience and Experimental Psychology (J.D.S.), Division of Neuroscience and Experimental Psychology (L.M.P.), Division of Cardiovascular Sciences, School of Medical Sciences (A.R.P.-J., C.J.S.), and Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care (A.V.), University of Manchester, Manchester Academic Health Science Centre, UK.

Objective: To explore the association between enzyme replacement therapy (ERT), clinical characteristics, and the rate of progression of white matter hyperintensities (WMH) in patients with Fabry disease (FD).

Methods: Patients with a confirmed diagnosis of FD, aged 18 years or older, participating in an existing FD observational study (NCT00196742), with at least 2 serial MRI brain scans at least 2 years apart for the period between December 2006 and August 2016 were included in this cohort study. Total WMH volume was estimated for each image using a semiautomated procedure. Read More

Clin Cardiol 2018 Sep 20;41(9):1207-1213. Epub 2018 Sep 20.

Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Canada.

Background: Fabry disease (FD) is a lysosomal storage disorder caused by an enzymatic deficiency. Conduction abnormalities and bradyarrhythmias are common and can occur prior to the onset of left ventricular (LV) hypertrophy. We aimed to describe the clinical, electrocardiographic and echocardiographic, including left atrial (LA) function, determinants of bradyarrhythmic events in FD. Read More

Medicine (Baltimore) 2018 May;97(21):e10669

Department of Internal Medicine I, Division of Cardiology and Nephrology and Comprehensive Heart Failure Center Würzburg, University Hospital Würzburg.

Single nucleotide polymorphisms (SNPs) in the alpha-galactosidase A gene region (GLA) have been discussed as potential cause of symptoms and organ manifestations similarly to those seen in Fabry disease (FD). However, due to scarce data, clinical implications remain limited. The aim of the present study was to investigate the clinical impact of -10C>T SNP in the GLA. Read More

Neurology 2018 Apr 21;90(16):e1379-e1385. Epub 2018 Mar 21.

From the Stroke Research Centre, Department of Brain Repair and Rehabilitation (P.P., A.M., I.D., X.G., D.J.W.), UCL Institute of Neurology; Charles Dent Metabolic Unit (A.M., E.M., R.H.L.), National Hospital for Neurology and Neurosurgery, London; Beaumont Hospital and Royal College of Surgeons in Ireland (A.M.), Beaumont, Dublin; Academic Department of Neuroradiology (I.D., X.G.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London; Department of Neuropsychology (F.B., L.C.), National Hospital for Neurology and Neurosurgery; Department of Biostatistics (F.J.), UCL and University College London Hospitals; Department of Neuroinflammation (C.W.-K.), UCL Institute of Neurology; and Lysosomal Storage Disorders Unit (D.H.), Royal Free Hospital, London, UK.

Objective: To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3.

Methods: This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. Read More

PLoS One 2018 5;13(4):e0193550. Epub 2018 Apr 5.

Lysosomal Storage Disorders Unit, Department of Haematology, Royal Free Hospital and University College Medical School, London, United Kingdom.

Background: Fabry disease (FD) results from X-linked inheritance of a mutation in the GLA gene, encoding for alpha galactosidase A, and is characterized by heterogeneous clinical manifestations. Two phenotypes have been described "Classic" and "late onset" which cannot be predicted exclusively by genotype. The latter has been considered an attenuated form of the disease often affecting a single organ system commonly the heart. Read More

Echocardiography 2018 05 19;35(5):643-650. Epub 2018 Feb 19.

Asociación Argentina de estudio de enfermedad de Fabry y otras enfermedades lisosomales.

Background: Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) are two diseases with a different pathophysiology, both cause left ventricular hypertrophy (LVH) and myocardial fibrosis. Although remodeling and systolic dysfunction of the left atrium (LA) are associated with atrial fibrillation and stroke in HCM, changes in the size and function of the LA have not been well studied in FD with LVH.

Methods: The following groups were studied prospectively, and their respective findings compared: 19 patients with non-obstructive HCM (Group I), 20 patients with a diagnosis of Fabry cardiomyopathy (Group II), and 20 normal subjects matched for sex and age (Group III). Read More

J Stroke Cerebrovasc Dis 2018 Mar 11;27(3):575-582. Epub 2017 Nov 11.

Academia de Medicina, Buenos Aires, Argentina.

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina.

Methods: This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Read More

Int J Cardiol 2017 Dec 19;249:261-267. Epub 2017 Sep 19.

Department of Internal Medicine, University Hospital of Zurich, Switzerland. Electronic address:

Aims: Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort.

Methods And Results: A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. Read More

Circ Cardiovasc Genet 2017 Aug;10(4)

From the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (B.A., R.P., R.A., G.T.G.); Division of Cardiology (B.A., R.D.), Department of Genetics (R.A.), Division of Nephrology (R.P.), and Department of Radiology (M.G.), Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Department of Cardiology, Haukeland University Hospital, Bergen, Norway (B.A.); Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.D., B.C., S.P.); Department of Genetics, Harvard Medical School, Boston, MA (P.T., M.A.B., J.G.S., C.E.S.); Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (E.A., U.N.); Division of Cardiology, Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, MA (M.M., B.J.M.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.A.B., C.E.S.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (M.A.B.); Department of Medical Endocrinology, Rigshospitalet and University of Copenhagen, Denmark (C.V.M., U.F.-R.); Howard Hughes Medical Institute, Boston, MA (C.E.S.); and Department of Medicine, Akureyri Hospital, Iceland (G.T.G.).

Background: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Read More

Semin Neurol 2017 06 31;37(3):351-365. Epub 2017 Jul 31.

Department of Neurology, University of Utah, Salt Lake City, Utah.

Stroke 2017 07 8;48(7):1766-1772. Epub 2017 Jun 8.

From the Division of Neurology, Department of Medicine, Hôpital du Sacré-Cœur de Montréal, Quebec, Canada (S.L.); Department of Neurosciences, Faculty of Medicine, University of Montreal, Quebec, Canada (S.L.); Stroke Outcomes Research Unit, Division of Neurology, Department of Medicine (G.S., D.S.), Department of Health Policy, Management and Evaluation (G.S.), Applied Health Research Centre (G.L., K.P.), St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada (G.L.); and Department of Neurology, University of North Dakota, Grand Forks (D.F.M.).

Background And Purpose: Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA).

Methods: We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation. Read More

BMJ Case Rep 2017 Jun 2;2017. Epub 2017 Jun 2.

Department of Neurology, Sir Charles Gairdner Hospital, Western Australian Neuromuscular Research Institute, Nedlands, Western Australia, Australia.

Fabry's disease (FD) is a recognised mimic of multiple sclerosis (MS). It is an X-linked storage lysosomal disorder with deficiency of α-galactosidase A and enzyme replacement therapy is available. Patients with FD may satisfy modified McDonald criteria if the diagnosis of FD has not been pursued. Read More

Rev Neurol 2017 May;64(10):454-458

Hospital Universitario de Torrejon, Torrejon de Ardoz, Espana.

Introduction: Fabry's disease is an infrequent metabolic pathology linked to the X chromosome which causes a wide variety of signs and symptoms.

Case Report: A 39-year-old male who was admitted to our stroke unit with right-side hemiparesis (1 + 0) and dysarthria (1). The score on the National Institute of Health Stroke Scale was 2. Read More

Ir J Med Sci 2018 Feb 3;187(1):189-192. Epub 2017 May 3.

Department of Neurology, Saint Vincent's University Hospital, Dublin, Ireland.

Background: Fabry disease is an X-linked recessive lysosomal storage disorder that provokes multi-organ morbidity, including early-onset stroke. Worldwide prevalence may be greater than previously estimated, with many experiencing first stroke prior to diagnosis of Fabry disease.

Aims: The aim of this study is to screen a cohort of stroke patients under 70 years of age, evaluating the clinical and economic efficacy of such a broad screening programme for Fabry disease. Read More

J Stroke Cerebrovasc Dis 2017 Jun 7;26(6):1334-1340. Epub 2017 Mar 7.

Department of Neurology, Sakarya University Training and Research Hospital, Sakarya, Turkey.

Background: Fabry disease (FD) is known as a rare cause of stroke. Recent studies suggested that FD is an underdiagnosed entity among young stroke patients. We aimed to investigate the frequency of FD in young cryptogenic stroke patients who lived in the City of Sakarya and to define the clinical features that help in recognizing patients with FD. Read More

Clin Genet 2017 Nov 24;92(5):528-533. Epub 2017 Apr 24.

Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Fabry disease (FD) is a multisystem lysosomal storage disorder caused by mutations in the GLA gene. The clinical significance of the mutation p.D313Y is still under debate. Read More

J Hum Genet 2017 Jul 9;62(7):665-670. Epub 2017 Mar 9.

Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.

Fabry disease is an important underlying disease in young cryptogenic stroke patients. However, little is known regarding the frequency of Fabry disease in the general stroke population, especially in elderly patients. A total of 588 stroke patients (61. Read More

Continuum (Minneap Minn) 2017 02;23(1, Cerebrovascular Disease):211-237

Purpose Of Review: This article is a practical guide to identifying uncommon causes of stroke and offers guidance for evaluation and management, even when large controlled trials are lacking in these rarer forms of stroke.

Recent Findings: Fabry disease causes early-onset stroke, particularly of the vertebrobasilar system; enzyme replacement therapy should be considered in affected patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), often misdiagnosed as multiple sclerosis, causes migraines, early-onset lacunar strokes, and dementia. Read More

Cerebrovasc Dis 2017 14;43(3-4):152-160. Epub 2017 Jan 14.

Department of Neurology, University Medicine, Ernst Moritz Arndt University, Greifswald, Germany.

Background: Although 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing.

Methods: In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI. Read More

J Am Soc Echocardiogr 2017 Mar 6;30(3):282-291. Epub 2017 Jan 6.

Department of Cardiovascular Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.

Background: Right ventricular (RV) involvement has been described in Anderson-Fabry disease (AFD), especially in patients with established Fabry cardiomyopathy (FC). However, few and controversial data on RV systolic function are available, and there are no specific tissue Doppler studies.

Methods: Detailed echocardiographic examinations were performed in 45 patients with AFD. Read More

J Am Soc Echocardiogr 2017 02 6;30(2):170-179.e2. Epub 2016 Dec 6.

Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, Canada. Electronic address:

Background: Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs, including the left atrium. It is uncertain if the left atrial (LA) reservoir, conduit, and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function.

Methods: In this retrospective cohort study, LA strain, strain rates, and phasic LA volumes were studied in 50 patients with FD and compared with values in 50 healthy control subjects. Read More

Stroke 2017 01 29;48(1):30-35. Epub 2016 Nov 29.

From the Department of Neurology, Medical Campus Lake Constance, Klinikum Friedrichshafen, Germany (R.H.); Department of Neurology, University of Ulm, Ulm, Germany (R.H.); Department for Biostatistics and Clinical Epidemiology (U.G.) and Center for Stroke Research (U.G.), Charité-Universitätsmedizin Berlin, Germany; Department of Internal Medicine II, Katharinen Hospital, Unna, Germany (F.W.); Department of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia (V.T.); Department of Neurology, Justus Liebig University Giessen, Germany (C.T.); Department of Neurology (C.E., F.F.) and Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology (C.E.), Medical University of Graz, Austria; Department of Neurology, University of Mannheim, Germany (M.W., M.G.H.); Department of Neurology and Stroke Service, The Adelaide and Meath Hospital, incorporating the National Children's Hospital, Dublin, Ireland (D.J.H.M.); Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, London, United Kingdom (D.J.H.M.); Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland (D.J.H.M.); Department of Neurology, Helsinki University Central Hospital, Finland (J.P., T.T.); Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (T.T.); Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Department of Neurology, University Medicine Greifswald, Ernst Moritz Arndt University of Greifswald, Germany (C.K., B.v.S.); Department of Epidemiology and Biometrics, University of Tübingen, Germany (P.M.); Department of Neurology, New York University School of Medicine (E.K.); Department of Clinical Sciences, Section of Neurology, Lund University, Sweden (B.N.); and Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Germany (A.R.).

Background And Purpose: A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. Read More

PLoS One 2016 11;11(11):e0166290. Epub 2016 Nov 11.

2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Background: Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD).

Objectives: To evaluate the association between serum UA levels and mortality and morbidity in FD. Read More

Zh Nevrol Psikhiatr Im S S Korsakova 2016;116(9):98-105

Vladimirsky Moscow Regional Research Institute, Moscow, Russia.

Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Read More

J Am Coll Cardiol 2016 09;68(10):1037-50

Center for Inherited Cardiovascular Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation University Hospital Policlinico San Matteo, Pavia, Italy. Electronic address:

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0. Read More

Pediatr Neurol 2016 11 29;64:10-20. Epub 2016 Jul 29.

Department of Pediatric Neurology and Metabolic Medicine, Center for Rare Disorders, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Background: Fabry disease, an X-linked disorder of glycosphingolipids, markedly increases the risk of systemic vasculopathy, ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction, and chronic kidney disease.

Methods: We performed an extensive PubMed search on the topic of Fabry disease and drew from our cumulative 43 years of experience.

Results: Most of these complications are nonspecific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Read More

Am J Med Genet A 2016 11 17;170(11):3051-3053. Epub 2016 Aug 17.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.

Mol Genet Metab 2016 09 13;119(1-2):151-9. Epub 2016 Jun 13.

Division of Medical Genetics, Department of Human Genetics, Emory University School of Medicine, Atlanta, USA. Electronic address:

Background: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death.

Methods: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. Read More

Mol Genet Metab 2016 09 22;119(1-2):144-50. Epub 2016 Jul 22.

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Fabry disease is a glycosphingolipid storage disorder that is caused by a genetic deficiency of the enzyme alpha-galactosidase A (AGA, EC 3.2.1. Read More

BMC Med Genet 2016 Jul 19;17(1):46. Epub 2016 Jul 19.

Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, Oberdürrbacher Str. 6, D-97080, Würzburg, Germany.

Background: X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. Read More

Ugeskr Laeger 2016 Jun;178(26)

Rare causes of ischaemic stroke comprise a plethora of diagnoses of cardioembolic, inflammatory and genetic origin. The differential diagnosis is challenging but important because these disorders (e.g. Read More

Stroke 2016 07 31;47(7):1702-9. Epub 2016 May 31.

From the Department of Cerebrovascular Disease, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy (A.B., G.B.B., E.A.P., N.T.); Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (H.S.M.); Department of Bio-Medical Informatics, University of Pavia, Pavia, Italy (S.Q.); Department of Inherited Cardiovascular Disease, Foundation IRCCS Policlinico San Matteo, Pavia, Italy (E.A., M.G.); Neurology Unit, Department of Neuroscience and Sensory Organs, Maggiore Policlinico Hospital Foundation IRCCS Ca' Granda, Milan, Italy (S.L., L.C.); Neurology and Stroke Unit, Department of Urgency (G.M., A.C.), Department of Genetics (C.C., G.G.), and Brain MRI 3T Research Center (P.V.), IRCCS Foundation Casimiro Mondino Neurological Institute, Pavia, Italy; Department of Genetics of Neurodegenerative and Metabolic Diseases, IRCCS Foundation C, Besta Neurological Institute, Milan, Italy (F.T., C.G., S.B.); Department of Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy (S.P., L.M.); Department of Genomics for Human Disease Diagnosis and Laboratory of Clinical Molecular Biology, IRCCS San Raffaele hospital, Milan, Italy (P.C., M.F.); University Vita-Salute, Milano, Italy (M.F.); Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy (S.C., D.R., G.P.C.); Neurology Unit, Department of Neuroscience and Sensory Organs, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico Milan, Milan, Italy (S.C., D.R., G.P.C.); Department of Molecular Biology, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy (M.T.B.); Center for amyloidosis, Department of medical Thecnologies, IRCCS Foundation San Matteo Policlinico, Pavia, Italy (L.O., G.M.); Vascular Neurology - Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (A. Pezzini, A. Padovani); Stroke Unit, Departmen

Background And Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease

Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. Read More

Neurology 2016 May 20;86(20):1880-6. Epub 2016 Apr 20.

From the J. Philip Kistler Stroke Research Center, Department of Neurology (N.S.R., L.C., A.S.K., K.M.F.), and the Center for Human Genetic Research, Department of Neurology (N.S.R., D.R.A., V.C., K.B.S.), Massachusetts General Hospital, Boston; Neurogenetics Unit (C.M.L.), School of Medicine of Riberirao Preto, University of São Paulo, Brazil; Division of Medical Genetics (D.P.G.), University of Versailles-St Quentin en Yvelines Paris-Saclay University, France; Fundación para el Estudio de las Enfermedades Neurometabólicas (FESEN) (J.M.P.), Buenos Aires, Argentina; and Departments of Neuroradiology (G.A.H.) and Neurology (C.S., N.Ü.), Fabry Center for Interdisciplinary Therapy (FAZIT) (C.S., N.Ü.), University of Würzburg, Germany.

Objective: Using a semiautomated volumetric MRI assessment method, we aimed to identify determinants of white matter hyperintensity (WMH) burden in patients with Fabry disease (FD).

Methods: Patients with confirmed FD and brain MRI available for this analysis were eligible for this protocol after written consent. Clinical characteristics were abstracted from medical records. Read More

Orphanet J Rare Dis 2016 05 4;11(1):54. Epub 2016 May 4.

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Albert-Schweitzer-Campus 1, D-48149, Muenster, Germany.

Background: Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma.

Methods: To determine the clinical impact of the alpha-Galactosidase A (GLA) p. Read More

Eur J Intern Med 2016 Jul 12;32:26-30. Epub 2016 Apr 12.

Periodic Fever Research Centre, A. Gemelli Policlinic, Catholic University of the Sacred Heart, Rome, Italy. Electronic address:

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme, which leads to the accumulation of its substrate, the globotriaosylceramide or Gb3, in many organs and tissues. Main clinical manifestations of FD are neuropathic pain, angiokeratomas, proteinuria and renal failure, left ventricular hypertrophy and stroke. Fever is also a possible symptom at the onset of the disease during childhood and adolescence, but it is frequently misdiagnosed, causing a delay in FD diagnosis. Read More

J Med Genet 2016 07 18;53(7):495-502. Epub 2016 Mar 18.

Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Read More

J Stroke Cerebrovasc Dis 2016 Jun 14;25(6):1320-5. Epub 2016 Mar 14.

Department of Neurology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Background And Purpose: Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with the central nervous system manifestations. Although white matter hyperintensity (WMH) on MRI has been previously reported, little is known about cerebral microbleeds (CMBs) in patients with FD. Our aim is to investigate the clinical characteristics of CMBs in patients with FD. Read More

Int J Neurosci 2017 Apr 4;127(4):350-355. Epub 2016 Apr 4.

a 1 Department of Neurology, Beijing Tsinghua Changgung Hospital , Beijing , China.

Purpose: Fabry disease is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. Data regarding Fabry disease and ischemic stroke has been lacking in China. In this study, we investigated the prevalence of Fabry disease and the distribution of the alpha-galactosidase A (α-GalA) gene - GLA mutations in young stroke patients in the Chinese population and its association with stroke subtypes. Read More

AJNR Am J Neuroradiol 2016 06 11;37(6):1044-9. Epub 2016 Feb 11.

School of Medicine (H.-J.L., S.-C.H., T.-R.H., S.-C.K., T.C.-M., C.-C.H., D.-M.N., C.-P.L.) Department of Biomedical Imaging and Radiological Sciences (S.-C.H., C.-C.H., C.-P.L.), National Yang-Ming University, Taipei, Taiwan.

Background And Purpose: A high incidence of cardiac-type Fabry disease with an α-galactosidase A mutation, IVS4 + 919 G>A, has been identified in the Taiwanese population. The neurologic manifestation has not been understood in this specific cardiac variant. This study aimed to investigate the typical imaging features of classic Fabry disease in patients with IVS4 Fabry disease. Read More

Zhonghua Yi Xue Za Zhi 2015 Jun;95(23):1829-32

Department of Neurology, Peking University First Hospital, Beijing 100034, China; Email:

Objective: To investigate incidence and clinical features of multiple organ involvement in Chinese patients with Fabry disease.

Methods: We collected 151 patients of 31 families with Fabry disease, all of whom were confirmed by classic pathology, decreased α-galactosidase A activity or GLA mutation from the year of 2011 to 2014 in Department of Neurology, Peking University First Hospital. The clinical data included incidence and onset of neuralgia, renal dysfunction, heart disease, hypertension and cerebral stroke. Read More

Joint Bone Spine 2016 Jul 14;83(4):421-6. Epub 2015 Dec 14.

Service de Rhumatologie, Médecine Interne, Site Diaconesses Croix St.-Simon, 125, rue d'Avron, 75020 Paris, France; Centre de Référence Maladies Lysosomales, Site Diaconesses Croix St.-Simon, 125, rue d'Avron, 75020 Paris, France.

Objectives: Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopathy, cardiac dysrhythmia, proteinuria, chronic kidney dysfunction, stroke, and hearing loss. Read More

BMC Neurol 2015 Dec 12;15:256. Epub 2015 Dec 12.

Department of Clinical and Experimental Medicine, University of Sassari, Viale S. Pietro, 10, 07100, Sassari, Italy.

Background: The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry's disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia. Read More

Intern Med 2015 1;54(23):3069-74. Epub 2015 Dec 1.

Division of Cardiology, Nephrology, Pulmonology, and Neurology, Department of Internal Medicine, Asahikawa Medical University, Japan.

Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. Read More

J Neurol 2016 Feb 14;263(2):257-262. Epub 2015 Nov 14.

Department of Neurology, New York University School of Medicine, New York, NY, USA.

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Read More

Handb Clin Neurol 2015 ;132:231-48

Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA. Electronic address:

Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Read More

PLoS One 2015 25;10(8):e0136352. Epub 2015 Aug 25.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Background And Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. Read More

J Stroke Cerebrovasc Dis 2015 Nov 19;24(11):2588-95. Epub 2015 Aug 19.

NEUROFARBA Department, University of Florence, v.le Pieraccini 6, 50139 Florence, Italy; Stroke Unit and Neurology, Heart and Vessels Department, Careggi Hospital, l.go Brambilla 3, 50134, Florence, Italy.

Background And Purpose: Cerebrovascular complications are often the first cause of hospitalization in patients with Fabry disease (FD). Screenings for FD among stroke patients have yielded discrepant results, likely as a result of heterogeneous or incomplete assessment. We designed a study to identify FD among adults 60 years of age or younger who were consecutively admitted for acute ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service in Italy. Read More

PLoS One 2015 14;10(8):e0135997. Epub 2015 Aug 14.

Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Background: Children and patients with cognitive deficits may find it difficult to understand the implication of research. In the European Union (EU), clinical studies outside the EU directives concerning medicinal products or medical devices, i.e. Read More

J Am Soc Nephrol 2016 Mar 16;27(3):952-62. Epub 2015 Jul 16.

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster,

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1. Read More

Praxis (Bern 1994) 2015 Jul;104(14):719-29

1 Klinik und Poliklinik für Innere Medizin, Universitätsspital Zürich.