Genotype, phenotype and disease severity reflected by serum LysoGb3 levels in patients with Fabry disease.
Mol Genet Metab
; 123(2): 148-153, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-28728877
ABSTRACT
BACKGROUND:
Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the α-galactosidase A (GLA) gene causing deficiency of α-galactosidase A which results in progressive glycosphingolipid accumulation, especially globotriaosylceramide (Gb3), in body liquids and lysosomes. In a large cohort of FD patients, we aimed to establish genotype/phenotype relations as indicated by serum LysoGb3 (deacylated Gb3).METHODS:
In 69 consecutive adult FD patients (males n=28 (41%)) with a GLA-mutation confirmed diagnosis, we conducted a multidisciplinary clinical characterization during their routine annual examinations, and measured serum LysoGb3 levels by high-sensitive electrospray ionization liquid chromatography tandem mass spectrometry.RESULTS:
Serum levels of LysoGb3 were significantly higher in Classic compared with Later-Onset phenotype and higher in the latter compared with controls, both in males (52 [40-83] vs 9.5 [4.5-20] vs 0.47 [0.41-0.61] ng/ml, P<0.001) and in females (9.9 [7.9-14] vs 4.9 [1.6-4.9] vs 0.41 [0.33-0.48] ng/ml, P<0.001), respectively. Multivariate linear regression analysis showed that LysoGb3 levels were independently associated with, serum creatinine (ß=0.09, 95%CI 0.04-0.13, P<0.001) and the presence of cardiomyopathy (ß=25, 95%CI 9.8-41, P=0.002). LysoGb3 levels were higher in males with frame-shift and nonsense mutations than in males with missense mutations (84 [72-109] vs 41 [37-52] ng/ml, P=0.002).CONCLUSION:
LysoGb3 relates to disease severity, enzyme replacement response, and to the genotype severity in males. LysoGb3 supports identifying patients at risk who require intensive monitoring and treatment. LysoGb3 appears to be one marker of metabolic phenotyping of FD.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esfingolípidos
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Índice de Severidad de la Enfermedad
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Glucolípidos
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Biomarcadores
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Enfermedad de Fabry
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Alfa-Galactosidasa
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Mutación
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Genet Metab
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Año:
2018
Tipo del documento:
Article