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Natural history of Sanfilippo syndrome in Spain
BACKGROUND: Mucopolysaccharidosis 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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879199/ https://www.ncbi.nlm.nih.gov/pubmed/24314109 http://dx.doi.org/10.1186/1750-1172-8-189 |
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author | Delgadillo, Verónica O’Callaghan, Maria del Mar Gort, Laura Coll, Maria Josep Pineda, Mercedes |
author_facet | Delgadillo, Verónica O’Callaghan, Maria del Mar Gort, Laura Coll, Maria Josep Pineda, Mercedes |
author_sort | Delgadillo, Verónica |
collection | PubMed |
description | BACKGROUND: Mucopolysaccharidosis 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: MPS 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. |
format | Online Article Text |
id | pubmed-3879199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38791992014-01-03 Natural history of Sanfilippo syndrome in Spain Delgadillo, Verónica O’Callaghan, Maria del Mar Gort, Laura Coll, Maria Josep Pineda, Mercedes Orphanet J Rare Dis Research BACKGROUND: Mucopolysaccharidosis 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: MPS 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. BioMed Central 2013-12-06 /pmc/articles/PMC3879199/ /pubmed/24314109 http://dx.doi.org/10.1186/1750-1172-8-189 Text en Copyright © 2013 Delgadillo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Delgadillo, Verónica O’Callaghan, Maria del Mar Gort, Laura Coll, Maria Josep Pineda, Mercedes Natural history of Sanfilippo syndrome in Spain |
title | Natural history of Sanfilippo syndrome in Spain |
title_full | Natural history of Sanfilippo syndrome in Spain |
title_fullStr | Natural history of Sanfilippo syndrome in Spain |
title_full_unstemmed | Natural history of Sanfilippo syndrome in Spain |
title_short | Natural history of Sanfilippo syndrome in Spain |
title_sort | natural history of sanfilippo syndrome in spain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879199/ https://www.ncbi.nlm.nih.gov/pubmed/24314109 http://dx.doi.org/10.1186/1750-1172-8-189 |
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