title: Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece.
abstract: Sanfilippo syndrome, or mucopolysaccharidosis type III (MPSIII) is a lysosomal storage disease with predominant neurological manifestations in affected children. It is considered heterogeneous with respect to prevalence, clinical presentation, biochemistry (four biochemical forms of the disease referred to as MPSIIIA, B, C, and D are known), and causative mutations. The perspective of therapeutic options emphasizes the need for better knowledge of MPSIII incidence and natural history. We performed parallel retrospective epidemiological studies of patients diagnosed with MSPIII in France (n = 128), UK (n = 126), and Greece (n = 20) from 1990 to 2006. Incidences ranged from 0.68 per 100,000 live-births in France to 1.21 per 100,000 live-births in UK. MPSIIIA, which predominates in France and UK, was absent in Greece, where most patients have MPSIIIB. The study confirmed the large allelic heterogeneity of MPSIIIA and MPSIIIB and detected several yet undescribed mutations. Analysis of clinical manifestations at diagnosis and over a 6-7 years follow-up indicated that almost all patients, whatever the disease subtype, expressed neurological manifestations before the age of 5 years, including language acquisition delay, cognitive delay, and/or abnormal behavior. In contrast to relatively homogeneous early onset manifestations, disease progression showed significant variation depending on subtype and age at diagnosis. Different severities of disease progressions and different allele distribution between France and UK suggested that mutations are not equally deleterious, although genotype-phenotype correlation could not be established. Notwithstanding the rapidity of further clinical deterioration, all MPSIII patients suffer early onset devastating neurological manifestations that deserve early treatment when available.
authors.affiliation: Hôpital Trousseau, Centre de référence des maladies lysosomales, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.forename: Yann
authors.initials: Y
authors.lastname: Mikaeloff
authors.forename: Roseline
authors.initials: R
authors.lastname: Froissart
authors.forename: Guillaume
authors.initials: G
authors.lastname: Caridade
authors.forename: Irène
authors.initials: I
authors.lastname: Maire
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillaud
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: François
authors.initials: F
authors.lastname: Feillet
authors.forename: Hélène
authors.initials: H
authors.lastname: Ogier
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zafeiriou
authors.forename: Lucy
authors.initials: L
authors.lastname: Lavery
authors.forename: Ed
authors.initials: E
authors.lastname: Wraith
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Heard
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005602:France / Q000453:epidemiology; D006115:Greece / Q000453:epidemiology; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D015994:Incidence; D007223:Infant; D008099:Liver / Q000378:metabolism; D009084:Mucopolysaccharidosis III / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase