Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30‐year period

Malm, Gunilla; Je, Månsson

doi:10.1111/j.1651-2227.2010.01800.x

Cited by 39 publications

(45 citation statements)

References 20 publications

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“…These findings contrast with previous retrospective studies which found MPS IIIA to be the most frequent type of Sanfilippo disease in northern Europe [19,32-34], whereas MPS IIIB is more frequent in southern Europe [35-38]. …”

Section: Discussioncontrasting

confidence: 99%

“…At 18 months of mean age, mild speech delay, without any new words was evident in most patients, corresponding to the onset of the first phase of the disease [2,4,5,19]. …”

Section: Discussionmentioning

confidence: 99%

“…However Meyer [10] and Valstar [7] revealed a significant correlation between the phenotype and genotype in patients affected by MPS IIIA [9,10]. In recent years, several studies from different countries have described the natural course of MPS III [9-12,14,19,20]. …”

Section: Introductionmentioning

confidence: 99%

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Natural history of Sanfilippo syndrome in Spain

Delgadillo

O’Callaghan

Gort

et al. 2013

Orphanet Journal of Rare Diseases

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BackgroundMucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulphate. Four MPS III types have been recognized, characterized by a large phenotypic heterogeneity. This is the first Spanish study describing the natural history of Sanfilippo patients (MPSIIIA, MPSIIIB and MPSIIIC), representing an essential step for understanding patient prognosis and for the establishment and application of future therapies.MethodsThis retrospective study aimed to establish the natural history of MPS III in Spain based on an extensive chronological data survey involving physicians and parents of 55 Spanish MPSIII patients. In addition to clinical description we report biochemical and molecular analysis already performed in the majority of cases.ResultsThe most frequent subtype was MPS IIIA (62%). Symptoms before diagnosis were speech delay in 85%, followed by coarse facial features in 78%, and hyperactivity in 65% of cases at a mean age of 3 years old. The median age at clinical and biochemical diagnosis for each MPS III subtype were as follows: IIIA 4.4 years (1.2 – 16 years), IIIB 3.1 years (1–29 years), and IIIC 6.3 years (3.4-22 years).45% of patients developed epilepsy at a median age of 8.7 (2.5 – 37) years old.Age of death for MPS IIIA patients was 15 years (11.5 – 26 years).Molecular analysis of our cohort reveals, as alluded to above, a great allelic heterogeneity in the three subtypes without clear genotype-phenotype correlations in most cases.ConclusionMPS IIIA is the most frequent subtype in Spanish Sanfilippo patients. Diagnosing physicians should consider Sanfilippo syndrome in children with non-specific speech delay, behavioural abnormalities, and/or mild dysmorphic features. We stress the importance of establishing early diagnosis procedures as soon as possible so as to be able to determine future short-term enzymatic or gene therapy treatments that can change the prognosis of the disease.

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Section: Discussioncontrasting

confidence: 99%

“…At 18 months of mean age, mild speech delay, without any new words was evident in most patients, corresponding to the onset of the first phase of the disease [2,4,5,19]. …”

Section: Discussionmentioning

confidence: 99%

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Natural history of Sanfilippo syndrome in Spain

Delgadillo

O’Callaghan

Gort

et al. 2013

Orphanet Journal of Rare Diseases

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“…The evaluations require a highly skilled clinical team with disease-specific expertise. Consistent with results of a previous study (Malm and Mansson 2010), we found that gross motor abilities are generally maintained longer than other skills, which results in a motor-driven active child with impaired cognition. The increased activity was commensurate and normal for a child of a corresponding developmental age.…”

Section: Discussionmentioning

confidence: 71%

Natural history of Sanfilippo syndrome type A

Buhrman

Thakkar

Poe

et al. 2013

J of Inher Metab Disea

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Sanfilippo type A is characterized by severe hearing loss and speech delay, followed by a rapid decline in cognitive skills by 3 years of age. Significant somatic disease occurs in more than half of patients. Behavioral difficulties presented between 2 and 4 years of age during a rapid period of cognitive decline. Gross motor abilities are maintained during this period, which results in an active child with impaired cognition. Sleep difficulties are concurrent with the period of cognitive degeneration. There is currently an unacceptable delay in diagnosis, highlighting the need to increase awareness of this disease among clinicians.

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“…The onset of both delayed cognitive development and abnormal behaviours occurs between approximately 3–4 years of age on average, though there is a great degree of variability [2, 5, 24, 27–30, 58, 60, 64]. In MPS IIIA, adaptive behaviour remained intact for longer than cognitive function in one study [60], but in a more recent study, children continued to acquire adaptive behaviour skills for longer than cognitive skills, though both declined after around 4 years [58].…”

Section: Recommendationsmentioning

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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Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30‐year period

Cited by 39 publications

References 20 publications

Natural history of Sanfilippo syndrome in Spain

Natural history of Sanfilippo syndrome in Spain

Natural history of Sanfilippo syndrome type A

Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III

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