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Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype.

Valstar MJ, Bruggenwirth HT, Olmer R, Wevers RA, Verheijen FW, Poorthuis BJ, Halley DJ, Wijburg FA - J. Inherit. Metab. Dis. (2010)

Bottom Line: 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 missense changes p.R643C, p.S612G, p.E634K, and p.L497V were exclusively found in patients with the attenuated phenotype.A key feature, necessitating metabolic studies, is the coexistence of behavioral problems.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Amsterdam Lysosome Center Sphinx, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT
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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Regression and survival in MPS IIIB patients of different phenotypes. Loss of walking indicates full loss of independent walking and loss of speech indicates full loss of speech
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Fig3: Regression and survival in MPS IIIB patients of different phenotypes. Loss of walking indicates full loss of independent walking and loss of speech indicates full loss of speech

Mentions: A remarkably large variability in the course of the disease was detected with an unusually mild course in the majority of patients (Fig. 3). Clinical phenotype could be assessed in 42 of the 44 patients for whom clinical data were available, since two patients, 2 and 4 years old at the time of the study, were excluded since no reliable phenotype could yet be assessed. These two patients were identified on the basis of hepatomegaly and developmental delay, respectively.Fig. 3


Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype.

Valstar MJ, Bruggenwirth HT, Olmer R, Wevers RA, Verheijen FW, Poorthuis BJ, Halley DJ, Wijburg FA - J. Inherit. Metab. Dis. (2010)

Regression and survival in MPS IIIB patients of different phenotypes. Loss of walking indicates full loss of independent walking and loss of speech indicates full loss of speech
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2992652&req=5

Fig3: Regression and survival in MPS IIIB patients of different phenotypes. Loss of walking indicates full loss of independent walking and loss of speech indicates full loss of speech
Mentions: A remarkably large variability in the course of the disease was detected with an unusually mild course in the majority of patients (Fig. 3). Clinical phenotype could be assessed in 42 of the 44 patients for whom clinical data were available, since two patients, 2 and 4 years old at the time of the study, were excluded since no reliable phenotype could yet be assessed. These two patients were identified on the basis of hepatomegaly and developmental delay, respectively.Fig. 3

Bottom Line: 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 missense changes p.R643C, p.S612G, p.E634K, and p.L497V were exclusively found in patients with the attenuated phenotype.A key feature, necessitating metabolic studies, is the coexistence of behavioral problems.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Amsterdam Lysosome Center Sphinx, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus