Mucopolysaccharidosis IIIB is caused by a marked decrease in N-acetyl-α-d-glucosaminidase (NAGLU) enzyme activity, which leads to the accumulation of heparan sulfate in key organs, progressive brain atrophy, and neurocognitive decline.
Autozygosity mapping was performed to identify the potential pathogenic variants in these 8 patients indirectly with the clinical diagnosis of MPSs. so three panels of STR (Short Tandem Repeat) markres flanking IDUA, SGSH and NAGLU genes were selected for multiplex PCR amplification.
Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years-three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA).
We have therefore developed an ex vivo haematopoietic stem cell gene therapy approach in a mouse model of mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid-specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU).
EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB.
RESOURCE DETAILS: Mucopolysaccharidosis IIIB (MPSIII, Sanfilippo syndrome type B) is a pediatric neurodegenerative disorder caused by a deficiency in NAGLU, an enzyme required for lysosomal degradation of heparin sulphate (HS).
It is classified as MPS type III, though it is caused by four different genetic defects, determining subtypes A, B, C and D. In each subtype of MPS III, the primary storage GAG is heparan sulfate (HS), but mutations leading to A, B, C, and D subtypes are located in genes coding for heparan N-sulfatase (the SGSH gene), α-N-acetylglucosaminidase (the NAGLU gene), acetyl-CoA:α-glucosaminide acetyltransferase (the HGSNAT gene), and N-acetylglucosamine-6-sulfatase (the GNS gene), respectively.
Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with complex CNS and somatic pathology due to a deficiency in α-N-acetylglucosaminidase (NAGLU).
Mucopolysaccharidosis IIIB (MPS IIIB) is a genetic disease characterized by mutations in the NAGLU gene, deficiency of α-N-acetylglucosaminidase, multiple congenital malformations and an increased susceptibility to malignancy.
No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease caused by autosomal recessive defect in α-N-acetylglucosaminidase (NAGLU).
To this end, we analyzed the UPR in vitro, in fibroblasts from patients with different types of mucopolysaccharidoses (MPS I, II, IIIA, IIIB, IVA) and in vivo, in the murine MPS IIIB model.
This led to the identification of compound heterozygous mutations in NAGLU, compatible with the diagnosis of Mucopolysaccharidosis IIIB (MPS IIIB or Sanfilippo Syndrome type B).
Recently, using a mouse model of mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological deterioration, we showed that MPS IIIB neuropathology is accompanied by a robust neuroinflammatory response of unknown consequence.
Identification and characterization of a novel homozygous deletion in the alpha-N-acetylglucosaminidase gene in a patient with Sanfilippo type B syndrome (mucopolysaccharidosis IIIB).
Mucopolysaccharidosis (MPS) type IIIC or Sanfilippo syndrome type C is a rare autosomal recessive disorder caused by the deficiency of the lysosomal membrane enzyme, heparan sulfate acetyl-CoA (AcCoA): alpha-glucosaminide N-acetyltransferase (HGSNAT; EC 2.3.1.78), which catalyzes transmembrane acetylation of the terminal glucosamine residues of heparan sulfate prior to their hydrolysis by alpha-N-acetylglucosaminidase.
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive disease that is caused by the deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU).
Sanfilippo syndrome type B [mucopolysaccharidosis IIIB (MPS IIIB] is the most prevalent type of MPS III in Greece, accounting for 81% of all MPS III cases diagnosed at the Institute of Child Health (Athens) over the last 20 years.
Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations.
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU).