Dataset Information


Residual N-acetyl-α-glucosaminidase activity in fibroblasts correlates with disease severity in patients with mucopolysaccharidosis type IIIB.

ABSTRACT: BACKGROUND:Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder in which the deficiency of the lysosomal enzyme N-acetyl-α-glucosaminidase (NAGLU) results in the accumulation of heparan sulfate (HS), leading to progressive neurocognitive deterioration. In MPS IIIB a wide spectrum of disease severity is seen. Due to a large allelic heterogeneity, establishing genotype-phenotype correlations is difficult. However, reliable prediction of the natural course of the disease is needed, in particular for the assessment of the efficacy of potential therapies. METHODS:To identify markers that correlate with disease severity, all Dutch patients diagnosed with MPS IIIB were characterised as either rapid (RP; classical, severe phenotype) or slow progressors (SP; non-classical, less severe phenotype), based on clinical data. NAGLU activity and HS levels were measured in patients' fibroblasts after culturing at different temperatures. RESULTS:A small, though significant difference in NAGLU activity was measured between RP and SP patients after culturing at 37 °C (p < 0.01). Culturing at 30 °C resulted in more pronounced and significantly higher NAGLU activity levels in SP patients (p < 0.001) with a NAGLU activity of 0.58 nmol.mg-1.hr-1 calculated to be the optimal cut-off value to distinguish between the groups (sensitivity and specificity 100 %). A lower capacity of patients' fibroblasts to increase NAGLU activity at 30 °C could significantly predict for the loss of several disease specific functions. CONCLUSION:NAGLU activity in fibroblasts cultured at 30 °C can be used to discriminate between RP and SP MPS IIIB patients and the capacity of cells to increase NAGLU activity at lower temperatures correlates with disease symptoms.


PROVIDER: S-EPMC4851702 | BioStudies | 2016-01-01

SECONDARY ACCESSION(S): 2013-001479-18

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5953891 | BioStudies
2019-01-01 | S-EPMC6606967 | BioStudies
2002-01-01 | S-EPMC1222624 | BioStudies
2018-01-01 | S-EPMC5833457 | BioStudies
2020-01-01 | S-EPMC7175334 | BioStudies
2015-01-01 | S-EPMC4493027 | BioStudies
2019-01-01 | S-EPMC6559735 | BioStudies
2018-01-01 | S-EPMC6215415 | BioStudies
2008-01-01 | S-EPMC2373330 | BioStudies
2013-01-01 | S-EPMC3695942 | BioStudies