Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease.

Background: Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD.

Methods: In 96 patients (53% female; age 40±12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire.

Gene mutations versus clinically relevant phenotypes: lyso-Gb3 defines Fabry disease.

Background: Currently, no method is available to identify α-galactosidase A (agalA) mutations determining clinically relevant Fabry disease. In our largest European Fabry cohort, we investigated whether a biomarker, specific for the defect, could stratify persons at risk.

Methods And Results: A total of 124 individuals with agalA mutations were investigated with a comprehensive clinical workup, genetic analysis, and laboratory testing, including measurements of agalA activity and lyso-Gb3 (degradation product of the accumulating Gb3).

Potential role of vitamin D deficiency on Fabry cardiomyopathy.

Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy.

Reproducibility of manual and semi-automated late enhancement quantification in patients with Fabry disease.

Background: Late enhancement (LE) imaging is increasingly used for diagnosis of non-ischemic cardiomyopathy. However, the mostly patchy appearance of LE in this context may reduce the reproducibility of LE measurement.

Purpose: To report intra- and inter-observer variabilities of LE measurements in Fabry disease using manual and semi-automated quantification.

Lyso-Gb3 Indicates that the Alpha-Galactosidase A Mutation D313Y is not Clinically Relevant for Fabry Disease.

The X-chromosomal-linked lysosomal storage disorder Fabry disease can lead to life-threatening manifestations. The pathological significance of the Fabry mutation D313Y is doubted, because, in general, D313Y patients do not present clinical manifestations conformable with Fabry disease. This is in contrast to the analysis of the alpha-galactosidase A activity, which is reduced in D313Y patients.

Cross-sectional baseline analysis of electrocardiography in a large cohort of patients with untreated Fabry disease.

Background: Morphology and function of Fabry cardiomyopathy has been previously studied by echocardiography and cardiac magnetic resonance (CMR). However, the value of electrocardiography (ECG) in relation to these two techniques remains largely unknown.

Methods: One hundred fifty genetically confirmed Fabry patients were investigated using a comprehensive clinical workup comprising 12-lead ECG, echocardiography, and CMR.

Cerebral blood flow in patients with Fabry disease as measured by Doppler sonography is not different from that in healthy individuals and is unaffected by treatment.

Objectives: The purpose of this study was to investigate cervical and cerebral blood flow characteristics in patients with Fabry disease at baseline and under enzyme replacement therapy.

Methods: In this case-control study we prospectively studied 68 patients with Fabry disease with extracranial and transcranial Doppler sonography. We compared extracranial and transcranial cervical and cerebral blood flow properties in all patients with Fabry disease and in subgroups of those with or without enzyme replacement therapy, male and female, and with normal or impaired renal function.

Small fibers in Fabry disease: baseline and follow-up data under enzyme replacement therapy.

Fabry disease (FD) is an X-linked lysosomal storage disorder which may lead to impaired peripheral nerve function, mostly affecting small nerve fibers, and to neuropathic pain. Characteristics of the neuropathy associated with FD and the covariates for its development and temporal course have not been described in a large cohort. We studied small fiber function and morphology in 120 Fabry patients at baseline and in subgroups of these until 4-year follow-up.

Interdisciplinary approach towards female patients with Fabry disease.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs.

Design: Being X-chromosomal-linked, most studies in the past have focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and thus need to be treated, respectively.

Tei index in fabry disease.

Background: Systolic and diastolic dysfunction of the left ventricle are present in patients with cardiac involvement in Fabry disease. The aim of this study was to investigate the diagnostic value of the Tei index, a marker for combined diastolic and systolic function, in patients with Fabry disease.

Methods: A total of 66 consecutive patients with genetically confirmed Fabry disease were included in this study.

A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy.

Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients.

Differences in Fabry cardiomyopathy between female and male patients: consequences for diagnostic assessment.

Objectives: We hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease.

Background: Fabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown.

MR-based analysis of regional cardiac function in relation to cellular integrity in Fabry disease.

Background: Fabry cardiomyopathy is characterized by left ventricular (LV) hypertrophy and regional fibrosis. Recent high-end echocardiography studies of selected LV sections suggest an interrelation between regional fibrosis, impaired function, and hypertrophy possibly changing under specific enzyme replacement therapy (ERT).

Methods: Magnetic resonance imaging (MRI) was used for a region dependent study of cardiac function, morphology and late enhancement (LE) in 25 Fabry patients before and after 12 months of ERT in comparison to 43 healthy volunteers.

Urinary total globotriaosylceramide and isoforms to identify women with Fabry disease: a diagnostic test study.

Background: Fabry disease is a treatable X-linked lysosomal storage disorder caused by alterations in the structural gene (GLA) of α-galactosidase A (AGAL), manifesting with cardiovascular and/or kidney disease and decreased life span. Although males as well as females can be affected, females cannot be identified using AGAL activity. We evaluated urinary total globotriaosylceramide (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female patients with and without chronic kidney disease (CKD).

Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A.

Aims: In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo (31)P-MR-spectroscopy.

Prominent papillary muscles in Fabry disease: a diagnostic marker?

Fabry disease is often linked with a prominent papillary muscle. It remains unknown whether this sign could be used as a diagnostic marker to screen for Fabry patients. Standard echo was performed in 101 consecutive patients with concentric left ventricular (LV) hypertrophy (28 Fabry, 30 Friedreich, 34 isolated arterial hypertension, 9 amyloidosis) and 50 healthy controls.

The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.

Background: Storage of globotriaosylceramides is present in the left and right ventricles of patients with Fabry disease. Improvement of left ventricular morphology and function during enzyme replacement therapy (ERT) has previously been reported.

Objectives: To analyse the effects of long term ERT on right ventricular morphology and function.

[Females with Fabry's disease - an interdisciplinary diagnostic and therapeutic challenge].

Fabry's disease is a rare genetic storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs. Being X-chromosomal-linked, most studies in the past focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and, thus, have to be treated respectively.

Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.

Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.

Department-related tasks and organ-targeted therapy in Fabry disease: an interdisciplinary challenge.

Fabry disease is a rare X-linked storage disorder leading to an accumulation of globotriaosylceramides in all cells carrying lysosomes. As the accumulation occurs in most organs, different medical specialties are involved in the diagnostics and therapy of Fabry disease. With this review of the 3 main specialties (cardiology, nephrology, and neurology) and, in addition, the adjacent specialties (ophthalmology and dermatology), we aim to discuss the division-related responsibilities and want to suggest an organ-related additional therapy besides enzyme replacement therapy.

Free breathing cardiac real-time cine MR without ECG triggering.

The increasing frequency of LV functional MRI studies demands for faster methods and for more comfort for the patient. We tested, whether real-time (RT) non ECG triggered MRI allows a considerable shortening of examination time in high reproducibility. RT and standard ECG-triggered breathhold cine MRI was acquired in 9 volunteers and 21 patients.

Dialysis and transplantation in Fabry disease: indications for enzyme replacement therapy.

ESRD is a major cause of morbidity and premature mortality in Fabry disease, particularly in classically affected males. The decline of renal function in Fabry nephropathy is adversely affected by male gender, advanced chronic kidney disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be missed if not specifically addressed in progressive CKD and patients have been first identified in screening programs of dialysis patients.

Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN).

Background: In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function.

Methods: An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases.

Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment.

Background: Enzyme replacement therapy with recombinant alpha-galactosidase A reduces left ventricular hypertrophy and improves regional myocardial function in patients with Fabry disease during short-term treatment. Whether enzyme replacement therapy is effective in all stages of Fabry cardiomyopathy during long-term follow-up is unknown.

Methods And Results: We studied 32 Fabry patients over a period of 3 years regarding disease progression and clinical outcome under enzyme replacement therapy.

[Division-related function and organ-related therapy in Fabry's disease. An interdisciplinary challenge].

Fabry's disease is a rare X-linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of all tissues. As the accumulation occurs in all organs, different medical faculties are involved in the diagnostics and therapy of Fabry's disease. With this review the three main faculties (cardiology, nephrology and neurology) as well as the adjacent faculties (ophthalmology and dermatology) want to discuss the division-related function and also to suggest an organ-related additional therapy besides enzyme replacement therapy.