A Multiplex Assay for the Diagnosis of Mucopolysaccharidoses and Mucolipidoses.
PLoS One
; 10(9): e0138622, 2015.
Article
em En
| MEDLINE
| ID: mdl-26406883
ABSTRACT
INTRODUCTION:
Diagnosis of the mucopolysaccharidoses (MPSs) generally relies on an initial analysis of total glycosaminoglycan (GAG) excretion in urine. Often the dimethylmethylene blue dye-binding (DMB) assay is used, although false-negative results have been reported. We report a multiplexed diagnostic test with a high sensitivity for all MPSs and with the potential to identify patients with I-cell disease (ML II) and mucolipidosis III (ML III).METHODS:
Urine samples of 100 treatment naive MPS patients were collected and analyzed by the conventional DMB assay and a multiplex assay based on enzymatic digestion of heparan sulfate (HS), dermatan sulfate (DS) and keratan sulfate (KS) followed by quantification by LC-MS/MS. Specificity was calculated by analyzing urine samples from a cohort of 39 patients suspected for an inborn error of metabolism, including MPSs.RESULTS:
The MPS cohort consisted of 18 MPS I, 16 MPS II, 34 MPS III, 10 MPS IVA, 3 MPS IVB, 17 MPS VI and 2 MPS VII patients. All 100 patients were identified by the LC-MS/MS assay with typical patterns of elevation of HS, DS and KS, respectively (sensitivity 100%). DMB analysis of the urine was found to be in the normal range in 10 of the 100 patients (sensitivity 90%). Three out of the 39 patients were identified as false-positive, resulting in a specificity of the LS-MS/MS assay of 92%. For the DMB this was 97%. All three patients with MLII/MLIII had elevated GAGs in the LC-MS/MS assay while the DMB test was normal in 2 of them.CONCLUSION:
The multiplex LC-MS/MS assay provides a robust and very sensitive assay for the diagnosis of the complete spectrum of MPSs and has the potential to identify MPS related disorders such as MLII/MLIII. Its performance is superior to that of the conventional DMB assay.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mucopolissacaridoses
/
Dermatan Sulfato
/
Heparitina Sulfato
/
Sulfato de Queratano
/
Mucolipidoses
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Humans
/
Infant
/
Middle aged
/
Newborn
Idioma:
En
Revista:
PLoS One
Ano de publicação:
2015
Tipo de documento:
Article