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Multicenter Study
. 2010 Dec;33(6):759-67.
doi: 10.1007/s10545-010-9199-y. Epub 2010 Sep 18.

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Marlies J Valstar  1 , Hennie T Bruggenwirth, Renske Olmer, Ron A Wevers, Frans W Verheijen, Ben J Poorthuis, Dicky J Halley, Frits A Wijburg
Affiliations
Multicenter Study

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Marlies J Valstar et al. J Inherit Metab Dis. 2010 Dec.

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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Figures

Fig. 1
Fig. 1
Flow diagram of MPS IIIB patients included in the study
Fig. 2
Fig. 2
Hazard curve of epilepsy in MPS IIIB patients (n = 43)
Fig. 3
Fig. 3
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
See this image and copyright information in PMC

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