Clinical variability in Sanfilippo B disease: a report on six patients in two related sibships

Kamp, J. J. P. Van De; Pelt, J.F. van; Liem, K. O.; Giesberts, M. A. H.; Niepoth, L. T. M.; Staalman, C. R.

doi:10.1111/j.1399-0004.1976.tb00049.x

Cited by 25 publications

(5 citation statements)

References 11 publications

(4 reference statements)

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“…This was previously reported in other studies on Dutch patients with MPS IIIB (Moog et al 2007; van de Kamp et al 1976; Verhoeven et al 2009). Patients with the classical severe phenotype of MPS III become completely dependent on external care and fully wheelchair dependent during their teenage years and usually die within the first two decades of life.…”

Section: Discussionsupporting

confidence: 83%

“…These 12 patients have been previously reported (Moog et al 2007; van de Kamp et al 1976, 1981; van Schrojenstein-de Valk and van de Kamp 1987). …”

Section: Resultsmentioning

confidence: 63%

“…Twenty-two patients from 12 families were previously reported in studies on MPS IIIB (Moog et al 2007; van de Kamp et al 1976; van Schrojenstein-de Valk and van de Kamp 1987; Verhoeven et al 2009). Family #19 consists of two closely related sibships (the fathers of these two sibships are brothers and the mothers are sisters).…”

Section: Resultsmentioning

confidence: 99%

“…However, another explanation might be a high degree of awareness of MPS III in the Netherlands leading to appropriate metabolic studies even in patients with a more attenuated phenotype. The studies on MPS III in the Netherlands by van der Kamp et al (1976, 1981) were conducted in close collaboration with a large number of physicians throughout the country. This may have increased awareness of the phenotypic spectrum of MPS III in the Netherlands.…”

Section: Discussionmentioning

confidence: 99%

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Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Valstar

Brüggenwirth

Olmer

et al. 2010

J of Inher Metab Disea

109

108

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Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disorder caused by deficiency of the enzyme N-acetyl-α-D-glucosaminidase (NAGLU). Information on the natural course of MPS IIIB is scarce but much needed in view of emerging therapies. To improve knowledge on the natural course, data on all 52 MPS IIIB patients ever identified by enzymatic studies in the Netherlands were gathered. Clinical data on 44 patients could be retrieved. Only a small number (n = 9; 21%) presented with a classical MPS III phenotype; all other patients showed a much more attenuated course of the disease characterized by a significantly slower regression of intellectual and motor abilities. The majority of patients lived well into adulthood. First signs of the disease, usually mild developmental delay, were observed at a median age of 4 years. Subsequently, patients showed a slowing and eventually a stagnation of development. Patients with the attenuated phenotype had a stable intellectual disability for many years. Molecular analysis was performed in 24 index patients. The missense changes p.R643C, p.S612G, p.E634K, and p.L497V were exclusively found in patients with the attenuated phenotype. MPS IIIB comprises a remarkably wide spectrum of disease severity, and an unselected cohort including all Dutch patients showed a large proportion (79%) with an attenuated phenotype. MPS IIIB must be considered in patients with a developmental delay, even in the absence of a progressive decline in intellectual abilities. A key feature, necessitating metabolic studies, is the coexistence of behavioral problems.

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Section: Discussionsupporting

confidence: 83%

“…These 12 patients have been previously reported (Moog et al 2007; van de Kamp et al 1976, 1981; van Schrojenstein-de Valk and van de Kamp 1987). …”

Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Valstar

Brüggenwirth

Olmer

et al. 2010

J of Inher Metab Disea

109

108

View full text Add to dashboard Cite

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

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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.

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Pathologic Findings in Mucopolysaccharidosis Type IIIB (Sanfilippo's Syndrome B)

Hadfield¹,

Ghatak²,

Nakoneczna³

et al. 1980

Archives of Neurology

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Clinical variability in Sanfilippo B disease: a report on six patients in two related sibships

Abstract: Two closely related sibships are described in which six definite and two probable patients with Sanfilippo B disease were found. The wide variation in phenotypic expression in these patients is suggestive of a genetic background effect.

Cited by 25 publications

References 11 publications

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

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

Pathologic Findings in Mucopolysaccharidosis Type IIIB (Sanfilippo's Syndrome B)

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