Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB)

Beesley, Clare E.; Jackson, Marie; Young, Elisabeth; Vellodi, Ashok; Winchester, Bryan

doi:10.1007/s10545-005-0093-y

Cited by 41 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, patients in early childhood have been misdiagnosed with idiopathic developmental delay, attention deficit/hyperactivity disorder, or autism spectrum disorders7). Progressive mental deterioration and loss of motor function usually occur after the first decade of life, but degree of mental regression varies among the patients189). The main long-term consequences of MPS III are loss of initiative and progressive motor retardation and subsequent early death in second or third decade of life1).…”

Section: Discussionmentioning

confidence: 99%

“…To date, more than 120 different disease-causing variants have been reported and the missense, small deletions, and insertions are common mutation types (www.hgmd.org). The R482W previously reported may have a founder effect in the Turkish populations69). Although the functional consequences of the mutation were not analyzed using an in vitro assay, D559Y is a highly conserved residue across various species by multiple sequence alignment using ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term clinical course of a patient with mucopolysaccharidosis type IIIB

et al. 2016

View full text Add to dashboard Cite

Mucopolysaccharidosis type III (MPS III) is a rare genetic disorder caused by lysosomal storage of heparan sulfate. MPS IIIB results from a deficiency in the enzyme alpha-N-acetyl-D-glucosaminidase (NAGLU). Affected patients begin showing behavioral changes, progressive profound mental retardation, and severe disability from the age of 2 to 6 years. We report a patient with MPS IIIB with a long-term follow-up duration. He showed normal development until 3 years. Subsequently, he presented behavioral changes, sleep disturbance, and progressive motor dysfunction. He had been hospitalized owing to recurrent pneumonia and epilepsy with severe cognitive dysfunction. The patient had compound heterozygous c.1444C>T (p.R482W) and c.1675G>T (p.D559Y) variants of NAGLU. Considering that individuals with MPS IIIB have less prominent facial features and skeletal changes, evaluation of long-term clinical course is important for diagnosis. Although no effective therapies for MPS IIIB have been developed yet, early and accurate diagnosis can provide important information for family planning in families at risk of the disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long-term clinical course of a patient with mucopolysaccharidosis type IIIB

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Only a small number of common mutations have been identified in MPS IIIB patients: the p.R279X and p.R626X associated to a severe phenotype. 17 MPS IIIC disorder is caused by deficiency of acetyl-CoA:a-glucosamide N-acetyltransferase caused by mutations in HSGNAT gene located at chromosome 8p11.1 and composed by 18 exons. From its recent cloning in 2006, only 60 mutations have been identified.…”

Section: Mucopolysaccharidosis Type III (Mps Iii)mentioning

confidence: 99%

Molecular Basis, Diagnosis and Clinical Management of Mucopolysaccharidoses

2013

View full text Add to dashboard Cite

Mucopolysaccharidoses (MPSs) are a group of hereditary, monogenic disorders caused by lysosomal storage of glycosaminoglycans. Their incidence as a group is between 1:25,000 and 1:45,000. At present 11 different enzyme deficiencies are know to be responsible of 7 similar but distinct diseases. The diagnosis is suspected clinically but must be confirmed through biochemical, enzymatic and molecular analysis. Prenatal diagnosis is feasible for each disease. The phenotype worsens with age, due to progressive storage, and mainly involves mucosal tissue, upper airways and lungs, bones and joints, central and peripheral nervous system, heart, liver, eye and ear. Any type of MPSs, is characterized by a wide variability of phenotype ranging from a severe fetal-neonatal disease to an attenuated form diagnosed in adult individuals. Recently new treatments, like hematopoietic stem cell transplantation and enzymatic replacement therapy, became available for many of these disorders entailing the urgency of early diagnosis to allow access to therapies. Thanks to therapies these patients have a longer life than in the past and this implies that also palliative treatments, of which the cardiological ones have a prominent part, must be undertaken diligently. The cardiologist may face, more frequently than expected, with the need to diagnose a patient with MPS who was not recognized by other specialists. The echocardiographic features of these patients are typical and may help in the clinical diagnosis. The future probably deserves to these disorders other new treatments or combination therapies, which might further improve prognosis of these diseases

show abstract

“…The gene encoding for NAGLU is localized on chromosome 17q21.1 (Zhao et al 1996) and over 100 mutations in the NAGLU gene (HGNC: 7632) have been identified (van de Kamp et al 1976; Beesley et al 1998, 2004, 2005; Schmidtchen et al 1998; Zhao et al 1998; Bunge et al 1999; Weber et al 1999; Esposito et al 2000; Tessitore et al 2000; Emre et al 2002; Chinen et al 2005; Champion et al 2010; Valstar et al 2010a; Ouesleti et al 2011; Selmer et al 2012; Tang et al 2013). Due to this large allelic heterogeneity, establishing a genotype-phenotype correlation is difficult.…”

Section: Introductionmentioning

confidence: 99%

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

Meijer

Welling

Valstar

et al. 2016

J of Inher Metab Disea

View full text Add to dashboard Cite

BackgroundMucopolysaccharidosis 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.MethodsTo 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.ResultsA 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.ConclusionNAGLU 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.

show abstract

Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB)

Cited by 41 publications

References 29 publications

Long-term clinical course of a patient with mucopolysaccharidosis type IIIB

Long-term clinical course of a patient with mucopolysaccharidosis type IIIB

Molecular Basis, Diagnosis and Clinical Management of Mucopolysaccharidoses

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

Contact Info

Product

Resources

About