High Variability of Fabry Disease Manifestations in an Extended Italian Family

Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. Thi...

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Bibliographic Details
Published in:BioMed research international 2015-01, Vol.2015 (2015), p.1-5
Main Authors: Nuzzo, Domenico, Monte, Ines, Bartolotta, Caterina, Zizzo, Carmela, Iemolo, Francesco, Sicurella, Luigi, Colomba, Paolo, Rodolico, Margherita Stefania, Fatuzzo, Pasquale, Cammarata, Giuseppe, Alessandro, Riccardo
Format: Article
Language:English
Subjects:
Adult
alpha-Galactosidase - genetics
Base Sequence
Colleges & universities
Deoxyribonucleic acid
Disease
DNA
DNA Mutational Analysis
Enzymes
Fabry Disease - enzymology
Fabry Disease - genetics
Fabry's disease
Family
Female
Females
Genetic testing
Hospitals
Humans
Italy
Male
Medical prognosis
Middle Aged
Molecular Sequence Data
Mutation
Pedigree
Physiological aspects
Young Adult
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Summary:Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.
ISSN:2314-6133
2314-6141
DOI:10.1155/2015/504784