Biomarkers of Fabry Disease Nephropathy

Abstract

It is suggested that biomarkers of renal complications of Fabry disease are likely to be useful for diagnosis and to follow the natural disease progression or the effect of specific therapeutic interventions. Traditionally, globotriaosylceramide (Gb 3 ) in urine has been used to evaluate the effect of specific therapy, such as enzyme replacement therapy (ERT). Although urinary Gb 3 decreases significantly with ERT, it has not yet been shown to be a valid surrogate marker in treatment trials. We propose a detailed study of the nature and origin of Gb 3 combined with a prospective collaborative trial that combines Gb 3 changes with the effect of ERT on clinical nephrological outcome measures. Existing biomarkers such as general proteinuria/ albuminuria or specific proteins such as N-acetyl-␤-D-glucosaminidase should be evaluated along with novel proteomic or metabolomic studies for biomarker discovery using mass spectrometry or nuclear magnetic resonance. Standard scoring of all pathologic aspects of kidney biopsies may also be a promising way to assess the effect of therapy.

Low frequency of Fabry disease in patients with common heart disease

“…13,14 Increased blood and urine Gb 3 and globotriaosylsphingosine (lyso-Gb 3 ) are considered important specific biomarkers in this disease, and are often used in screening and diagnosis for this disorder. 15,16 Since cardiac manifestations of Fabry disease are common and largely non-specific in their clinical presentation, we screened for this disorder in patients with common heart disease. We hypothesized that there are patients with undiagnosed Fabry disease, particularly with later-onset mutations, among patients with all forms of heart disease seen in the general population, although the incidence may be higher in more specific types of heart disease, such as hypertrophic cardiomyopathy.…”

Study of urinary proteomes in Anderson-Fabry disease

“…13 However, there is a critical need to find new biomarkers for assessment of the disease severity and the ERT efficacy. 14 Our study was designed to analyze potential differences in urinary proteomes between AFD patients and healthy controls, using modern analytical techniques, such as isoelectric focusing and two-dimensional (2D) electrophoresis in polyacrylamide gels. Employment of a similar technique of protein determination by 2D electrophoresis was shown in previous studies, [15][16][17][18] in which some protein differences specific to certain diagnoses (nephrotic syndrome, Fanconi syndrome, or various carcinomas) were detected.…”

Tandem Mass Spectrometry of Sphingolipids: Application in Metabolic Studies and Diagnosis of Inherited Disorders of Sphingolipid Metabolism

“…Our tests in a group of Fabry male-patients showed however, that monitoring of this marker is not informative for all treated patients in general but for individual patients only (data not shown). Although excreted Gb3Cer is useful parameter for diagnosis, it is not reliable biomarker for clinical trials as also confirmed by another studies (Schiffmann, et al, 2010). Biological basis of urinary Gb3Cer and its isoforms is still subject of research.…”