Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

Aims: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under 'real-world' conditions.

Diffusion tensor imaging reveals changes in non-fat infiltrated muscles in late onset Pompe disease.

MRI is a helpful tool for monitoring disease progression in late-onset Pompe disease (LOPD). Our study aimed to evaluate if muscle diffusion tensor imaging (mDTI) shows alterations in muscles of LOPD patients with <10% fat-fraction. We evaluated 6 thigh and 7 calf muscles (both legs) of 18 LOPD and 29 healthy controls (HC) with muscle diffusion tensor imaging (mDTI), T1w, and mDixonquant sequences in a 3T MRI scanner.

Analysis of Renal and Cardiac Outcomes in Male Participants in the Fabry Outcome Survey Starting Agalsidase Alfa Enzyme Replacement Therapy Before and After 18 Years of Age.

Purpose: To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for ≤10 years after ERT initiation in males from the Fabry Outcome Survey (FOS).

Patients And Methods: Male patients from FOS were stratified into three cohorts by age at ERT initiation: ≤18 years (cohort 1), >18 and ≤30 years (cohort 2), and >30 years (cohort 3). Analysis included age at symptom onset, diagnosis, and ERT initiation; ERT duration; FOS-Mainz Severity Score Index (FOS-MSSI); estimated glomerular filtration rate (eGFR); proteinuria level; and left ventricular mass indexed to height (LVMI).

Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS).

Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α-Gal A activity. We assessed safety along with cardiovascular, renal, and patient-reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under "real-world" conditions.

Extent, impact, and predictors of diagnostic delay in Pompe disease: A combined survey approach to unveil the diagnostic odyssey.

Background: Early diagnosis is of substantial benefit for patients with Pompe disease. Yet underdiagnosing and substantial diagnostic delay are still frequent and the determinants of this are unknown. This study is the first to systematically investigate the diagnostic odyssey in Pompe disease from patients', parents', and physicians' perspectives.

Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease.

Background: The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines.

Methods: Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.

D313Y mutation in the differential diagnosis of white matter lesions: Experiences from a multiple sclerosis outpatient clinic.

White matter lesions (WML) in younger patients might be due to a variety of neurological disorders. Fabry disease (FD), an x-linked inherited lysosomal storage disorder, happens to be misdiagnosed as multiple sclerosis (MS). In two middle-aged female patients, presenting bilateral WML, diagnosis of MS turned out to be doubtful.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.

Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory.

Ocular signs correlate well with disease severity and genotype in Fabry disease.

Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination.

CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy.

Purpose: Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) prolongs survival in infantile Pompe disease (IPD). However, the majority of cross-reactive immunologic material (CRIM)-negative (CN) patients have immune responses with significant clinical decline despite continued ERT. We aimed to characterize immune responses in CN patients with IPD receiving ERT monotherapy.

Thromboembolic events in Fabry disease and the impact of factor V Leiden.

Objectives: Although several reports suggest an increased thromboembolic event rate, especially regarding strokes and TIAs at early age in patients with Fabry disease (FD), the risk for patients with FD to experience these events, the clinical relevance of additional risk factors including the concurrence of factor V Leiden (FVL), and the benefit of enzyme replacement therapy (ERT) regarding these events remain unclear.

Methods: Three hundred four consecutively recruited patients with FD were evaluated for their lifetime occurrence of thromboembolic events such as stroke, TIA, deep vein thrombosis, and pulmonary embolism. The thromboembolic risk was determined in patients with FD and concurrent FVL, and the impact of ERT was assessed.

Outcome of patients with classical infantile pompe disease receiving enzyme replacement therapy in Germany.

Purpose: Enzyme replacement therapy (ERT) has been shown to improve outcome in classical infantile Pompe disease. The purpose of this study was to assess mortality, morbidity, and shortcomings of ERT in a larger cohort of patients treated outside clinical trials. To accomplish this, we retrospectively analyzed the data of all 23 subjects with classical infantile Pompe disease having started ERT in Germany between January 2003 and December 2010.

Urge incontinence and gastrointestinal symptoms in adult patients with pompe disease: a cross-sectional survey.

Objective: To determine the frequency and impact of gastrointestinal symptoms, and bowel and urinary incontinence, as this is currently unknown in adults with Pompe disease.

Methods: Adult German Pompe patients and age- and gender-matched controls were asked about symptoms in the upper and lower intestinal tract as well as urinary incontinence using the Gastrointestinal Symptoms Questionnaire and the International Consultation on Incontinence Questionnaires for Bowel Symptoms and Urinary Incontinence.

Results: The overall response rate was 78%; 57 patients and 57 controls participated.

Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis type VI rats and comparison to oral treatment.

Background: We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (s.c.

Pregnancy and delivery in women with Pompe disease.

Background: The obstetric risk in patients with Pompe disease (glycogen storage disease type II), a mainly skeletal muscle disorder, is unknown.

Methods: The clinical course and the outcome of pregnancy, and the effect of pregnancy on disease manifestations or clinical signs and symptoms in Pompe disease were analyzed retrospectively using a questionnaire. Participating women with Pompe disease were recruited by the German and the UK sections of the International Pompe Association, and by centers associated within the German Pompe Group.

Mucopolysaccharidoses and other lysosomal storage diseases.

Mucopolysaccharidosis and other lysosomal storage diseases are rare, chronic, and progressive inherited diseases caused by a deficit of lysosomal enzymes. Patients are affected by a wide variety of symptoms. For some lysosomal storage diseases, effective treatments to arrest disease progression, or slow the pathologic process, and increase patient life expectancy are available or being developed.

A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations.

Background: Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.