Method for the Diagnosis of Metachromatic Leukodystrophy

Abstract

The present invention is related to a method for diagnosing metachromatic leukodystrophy in a subject comprising a step a), wherein the step a) comprises detecting a biomarker in a sample from the subject, wherein the sample is selected from the group consisting of blood, dried blood, serum and plasma and wherein the biomarker is different from an enzyme.

1 . A method for diagnosing metachromatic leukodystrophy in a subject comprising
 a step a), wherein the step a) comprises detecting a biomarker in a sample from the subject, wherein the sample is selected from the group consisting of blood, dried blood, serum and plasma and wherein the biomarker is different from an enzyme.   
     
     
         2 . The method according to  claim 1 , wherein the enzyme is selected from the group comprising arylsulfatase A, N-acetyl-alpha-glucosaminidase, arylsulfatase and beta-glucuronidase. 
     
     
         3 . The method according to  claim 1 , wherein the sample is a serum sample of the subject, a plasma sample of the subject or a dried blood sample of the subject. 
     
     
         4 . The method according to  claim 1 , wherein the method comprises
 a step b) wherein the step b) comprises determining a level of the biomarker present in the sample.   
     
     
         5 . The method according to  claim 1 , wherein the level of the biomarker is indicative whether or not the subject is suffering from metachromatic leukodystrophy or whether or not the subject is at risk of suffering from metachromatic leukodystrophy. 
     
     
         6 . The method according to  claim 1 , wherein the biomarker is detected by means of immunoassay, mass spectrometric analysis, biochip array, functional nucleic acids and/or a fluorescent derivative of the biomarker. 
     
     
         7 . The method according to  claim 6 , wherein the biomarker is detected by means of mass spectrometric analysis, optionally combined with HPLC. 
     
     
         8 . The method according to  claim 7 , wherein mass spectrometric analysis is selected from the group comprising SELDI, MALDI, MALDI-Q TOF, MS/MS, TOF-TOF and ESI-O-TOF. 
     
     
         9 . The method according to  claim 7 , wherein the mass spectrometric analysis comprises or uses MS/MS. 
     
     
         10 . The method according to  claim 1 , wherein the biomarker is free lyso-Gb1-sulfatide, wherein lyso-Gb1-sulfatide is of formula (I) 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method according to  claim 1 , wherein step b) comprises comparing the level of the biomarker in the sample from the subject with a cut-off value. 
     
     
         12 . The method according to  claim 11 , wherein the cut-off value for free lyso-Gb1-sulfatide is 0.05 ng/ml. 
     
     
         13 . The method according to  claim 1 , wherein if the level of the biomarker in the sample from the subject is higher than the cut-off value, this is indicative that the subject is suffering from metachromatic leukodystrophy or is at risk of suffering from metachromatic leukodystrophy; whereas if the level of the biomarker in the sample from the subject is lower than the cut-off value, this is indicative that the subject is not suffering from or is not at risk of suffering from metachromatic leukodystrophy. 
     
     
         14 . The method according to  claim 12 , wherein the method used in the detection and/or determination of the level of the biomarker present in the sample, has a limit of determination for free lyso-Gb1-sulfatide of 0.05 ng/ml. 
     
     
         15 . Use of a biomarker for the diagnosis of metachromatic leukodystrophy, preferably in a method according to  claim 1 , wherein the biomarker is free lyso-Gb1-sulfatide. 
     
     
         16 . Use of mass spectrometric analysis for the detection of a biomarker, wherein the biomarker is free lyso-Gb1-sulfatide and the mass spectrometric analysis preferably comprises or uses MS/MS. 
     
     
         17 . Use according to  claim 16 , wherein the biomarker is detected in a sample from a subject, whereby the sample is selected from the group consisting of a plasma sample from the subject, a serum sample from the subject and a dried blood sample from the subject. 
     
     
         18 . Use according to  claim 16 , wherein mass spectrometric analysis is combined with HPLC. 
     
     
         19 . A kit for determining the presence of a biomarker in a sample from a subject, wherein the kit comprises
 a) an interaction partner of the biomarker;   b) optionally a solid support comprising at least one capture reagent attached thereto, wherein the capture reagent binds the biomarker, and   c) instructions for using the solid support to detect the biomarker,   wherein the biomarker is free lyso-Gb1-sulfatide.   
     
     
         20 . The kit according to  claim 19 , wherein the sample is selected from the group consisting of a plasma sample from the subject, a serum sample from the subject and a dried blood sample from the subject.