Usefulness of lyso-globotriaosylsphingosine in dried blood spots in the differential diagnosis between multiple sclerosis and Anderson-Fabry's disease.

Autor: Olivera S; Unit of Rare Disorders, Department of Internal Medicine, Lozano Blesa; University Hospital. Zaragoza. Spain; IISAragon, Hospital, Universitario Lozano Blesa, Zaragoza, Spain., Iñiguez C; Unit of Multiple Sclerosis, Department of Neurology.Lozano Blesa University Hospital. Zaragoza. Spain., García-Fernández L; Unit of Multiple Sclerosis, Department of Neurology.Lozano Blesa University Hospital. Zaragoza. Spain., Sierra JL; Unit of Rare Disorders, Department of Internal Medicine, Lozano Blesa; University Hospital. Zaragoza. Spain; IISAragon, Hospital, Universitario Lozano Blesa, Zaragoza, Spain., Camón AM; Unit of Rare Disorders, Department of Internal Medicine, Lozano Blesa; University Hospital. Zaragoza. Spain; IISAragon, Hospital, Universitario Lozano Blesa, Zaragoza, Spain., Menao S; Unit of Rare Disorders, Department of Internal Medicine, Lozano Blesa; University Hospital. Zaragoza. Spain; Department of Biochemistry, Lozano Blesa' University Hospital, Zaragoza. Spain., Torralba MÁ; Unit of Rare Disorders, Department of Internal Medicine, Lozano Blesa; University Hospital. Zaragoza. Spain; IISAragon, Hospital, Universitario Lozano Blesa, Zaragoza, Spain. Electronic address: matorralba@salud.aragon.es.
Jazyk: angličtina
Zdroj: Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2020 Feb; Vol. 38, pp. 101466. Date of Electronic Publication: 2019 Oct 23.
DOI: 10.1016/j.msard.2019.101466
Abstrakt: Background: The presence of white mater lesions in the central nervous system forces the differential diagnosis between multiple sclerosis (MS) and Anderson-Fabry disease (FD). Due to the type of inheritance, linked to the X chromosome, the diagnosis of FD is especially difficult in women. Tissue´s deposits of globotriaosylceramide (Gb3) are characteristics for FD and the deacylated form of Gb3 (Globotriaosylsphingosine or LysoGb3) is specific for this entity. Our objective is to investigate if concentrations of plasma Lyso-Gb3 are useful for ruling out the FD in a Spanish cohort of patients with a previous diagnosis of MS.
Methods: we evaluated the α-galactosidase A enzymatic activity in 154 patients with a previous diagnosis of MS (93 women and 61 men): 103 Relapsing Remitting MS patients, 19 progressive MS patients and 32 with the clinically isolated syndrome. 116 (75% of the patients) were on MS disease modifying therapy. Enzymatic assay was completed in all cases and done on dried blood spot (DBS) samples. Subsequently the GLA gene was sequenced only in males and females who presented an enzymatic assay significantly lower than standardized controls (<50% for men and <75% for women). For subjects with GLA variants, plasma Lyso-Gb3 levels were performed by Tandem mass spectrometry from DBS, assuming a cut-off point for normality <3.5 ng/mL.
Results: Genetic study was carried out in 30 women and 7 men; 8 of them had non-previous described GLA variants. After a thorough clinical examination no organic disease was found in any of the classical target organs. The study of Lyso-Gb3 concentrations in DBS was lower than 3.5 ng/mL, allowing us to discharge FD in all subjects and to consider these GLA variants like non pathologic.
Conclusions: Lyso-Gb3 concentration in DBS is a useful tool to rule out Fabry disease in patients with MS. A concentration of LysoGb3 < 3.5 ng/mL rules out FD.
Competing Interests: Declaration of Competing Interest Dr Torralba serves as a consultant for Genzyme Corporation and Shire Company and has received research grants, travel support and honoraria for speaking engagements from both companies. Dr Iñiguez has received research grants, travel support and honoraria for speaking engagements from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. The rest of the authors declare the absence of conflict of interests.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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