Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C)

Kamp, J. J. P. Van De; Niermeijer, M. F.; Figura, Kurt Von; Giesberts, M. A. H.

doi:10.1111/j.1399-0004.1981.tb01821.x

Cited by 171 publications

(35 citation statements)

References 13 publications

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“…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: 64%

“…This allelic heterogeneity likely causes the wide spectrum of clinical phenotypes observed in MPS IIIB (Weber et al 1999), mainly characterized by a remarkable variability in the rate of progression (Moog et al 2007; van de Kamp et al 1981; van Schrojenstein-de Valk and van de Kamp 1987; Verhoeven et al 2009). However, unbiased information on the natural course of MPS IIIB is limited.…”

Section: Introductionmentioning

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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“…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: 64%

Section: Introductionmentioning

confidence: 99%

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

“…Recurrent ENT infections and diarrhoea are common symptoms and a significant number of patients undergo adenoidectomy or tonsillectomy [60]. Umbilical or inguinal hernias are frequently reported [25, 29, 30]. Multiple skeletal manifestations have been described, particularly hip dysplasia and osteonecrosis of the femoral head [23, 61, 62].…”

Section: Recommendationsmentioning

confidence: 99%

“…However, there is a great degree of variability both within and between subtypes [25, 27]. Very attenuated phenotypes have been reported, usually in association with specific mutations [30–34].…”

Section: Introductionmentioning

confidence: 99%

Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III

Ghosh

Shapiro

Rust

et al. 2017

Orphanet J Rare Dis

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BackgroundMucopolysaccharidosis type III is a progressive, neurodegenerative lysosomal storage disorder for which there is currently no effective therapy. Though numerous potential therapies are in development, there are several challenges to conducting clinical research in this area. We seek to make recommendations on the approach to clinical research in MPS III, including the selection of outcome measures and trial endpoints, in order to improve the quality and impact of research in this area.ResultsAn international workshop involving academic researchers, clinical experts and industry groups was held in June 2015, with presentations and discussions on disease pathophysiology, biomarkers, potential therapies and clinical outcome measures. A set of recommendations was subsequently prepared by a working group and reviewed by all delegates. We present a series of 11 recommendations regarding the conduct of clinical research, outcome measures and management of natural history data in Mucopolysaccharidosis type III.ConclusionsImproving the quality of clinical research in Mucopolysaccharidosis type III will require an open, collaborative and systematic approach between academic researchers, clinicians and industry. Natural history data should be published as soon as possible and ideally collated in a central repository. There should be agreement on outcome measures and instruments for evaluation of clinical outcomes to maximise the effectiveness of current and future clinical research.

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“…Similar rates are documented internationally (Valstar et al 2008), although subtype B is known to be more common in South East Europe (Heron et al 2010). Clinically, there is very little difference between the subtypes, but subtype A is known to follow a more severe course (Van De Kamp et al 1981) and subtype C a more attenuated course (Ruijter et al 2008). …”

Section: Introductionmentioning

confidence: 99%

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review

Wolfenden

Wittkowski

Hare

2017

J Autism Dev Disord

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The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.

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Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C)

Cited by 171 publications

References 13 publications

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review

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