<p>Diagnosis and Screening of Patients with Fabry Disease</p>

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by absence or deficient activity of α-galactosidase A (α-Gal A) due to mutations in the α-galactosidase A gene (GLA), leading to progressive accumulation of globotriaosylceramide (Gb3) in tissues and organs including heart, kidney, the eyes, vascular endothelium, the nervous system and the skin. Cardiac involvement is leading to fatal complications and reduced life expectancy. FD is treatable with disease-specific treatment (enzyme replacement therapy (ERT) or with chaperone therapy). Therefore, the early diagnosis of FD is crucial for reducing the morbidity and mortality. Screening of high-risk populations (eg, patients with unexplained left ventricular hypertrophy (LVH), young patients with unexplained stroke, and patients with unexplained renal failure proteinuria or microalbuminuria) yields good results. The diagnostic algorithm is gender-specific. Initially, the measurement of α-Gal A activity is recommended in males, and optionally in females. In males with non-diagnostic residual activity (5-10%) activity, genetic testing is afterwards done for confirming the diagnosis. In fact, diagnosis of FD is not possible without genetic testing for both males and females. Globotriaosysphingosine (lyso-Gb3) for identification of atypical FD variants and highsensitive troponin T (hsTNT) for identification of cardiac involvement are also important diagnostic biomarkers. The aim of this review was to provide an update on diagnosis and screening of patients with FD.

Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

“…A particular mentioning for genetic investigations is worth in the diagnostic workup: indeed genetics is in rapid evolution and has radically modified the approach to rare diseases in recent years [ 1 , 5 , 6 ]. In particular, the recent availability of next generation sequencing has deeply revolutioned the scenario of INMD, compared to only a few years ago, when the diagnostic algorithms were based on the sequencing gene by gene (e.g., Sanger), based on clinical, neurophysiology, biochemical and morphological evaluations [ 1 ].…”

“…The diagnostic algorithm in FD is gender-specific indeed the measurement of blood α-Gal A activity is recommended in males, and optionally in females. Globotriaosysphingosine for identification of atypical FD variants and high- sensitive troponin T for identification of cardiac involvement are also important diagnostic biomarkers [ 6 ].…”

Fabry disease: what the cardiologist should consider in non-cardiac screening, diagnosis, and management—narrative review

“…Diagnostics in the centre include anamnesis with pedigree preparation, clinical examination, laboratory testing, genetic testing, and various imaging procedures (34)(35)(36).…”

Fabry Cardiomyopathy: Current Treatment and Future Options

“…Typical manifestations include neuropathic pain, telangiectasias, anhidrosis, gastrointestinal symptoms, cornea verticillata, renal failure with unknown etiology, unexplained left ventricular (LV) hypertrophy or neurological manifestations (e.g., cryptogenic stroke) [3][4][5][6][7][8]. Regarding diagnosis of FD and Fabry cardiomyopathy, various reviews have been published [9,10].…”

“…In suspected cases, determination of GLA activity is recommended. In males, GLA activity <1% is highly suggestive for the disease of classic FD [9]. In females and in patients with late-onset mutations (e.g., N215S cardiac variant mutation) the enzyme activity may be residual or even normal; thus, in such cases, genetic testing of Fabry mutations is mandatory [11].…”