title: 12 year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: the important role of early treatment.
abstract: BACKGROUND
  Mucopolysaccharidosis type I is an autosomal recessive disorder caused by deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, Mucopolysaccharidosis type I is classified into two forms: severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement and attenuated (Hurler/Scheie and Scheie syndromes), which presents with slower progression and absent to mild nervous system involvement. The specific treatment for attenuated Mucopolysaccharidosis type I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present here the clinical and laboratory results in an 12-year-old patient affected by the attenuated form of Mucopolysaccharidosis type I treated by enzyme-replacement therapy from the age of 5 months, compared with his 17 year old affected sister, who started therapy at 5 years of age.
  
  
  METHODS
  Clinical evaluation of these siblings shows that initiation of therapy prior of the onset of clinically detectable disease resulted in considerable improvement in outcome in the young sibling. After 12 years of enzyme-replacement therapy, facial appearance, linear growth rate, and liver and spleen volumes were normal; moreover, the degree of joint disease, vertebral, and cardiac valvular involvement were only minimal compared with those of his sister.
  
  
  CONCLUSIONS
  This study demonstrates that early diagnosis and early initiation of enzyme-replacement therapy substantially modify the natural history of the attenuated form of Mucopolysaccharidosis type I.
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Via Corridoni 11, 60123, Ancona, Italy. o.gabrielli@mercurio.it.
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.affiliation: Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Clarke
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Via Corridoni 11, 60123, Ancona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ficcadenti
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Via Corridoni 11, 60123, Ancona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Via Corridoni 11, 60123, Ancona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Zampini
authors.affiliation: Department of Biology, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Volpi
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Via Corridoni 11, 60123, Ancona, Italy.
authors.forename: Giovanni V
authors.initials: GV
authors.lastname: Coppa
mesh_terms: D000293:Adolescent; D002648:Child; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000097:blood / Q000652:urine; D006801:Humans; D007068:Iduronidase / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D008059:Mucopolysaccharidosis I / Q000235:genetics* / Q000628:therapy*; D011788:Quality of Life; D013154:Spleen / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D007068:Iduronidase
keywords: Attenuated Mucopolysaccharidosis type I; Enzyme replacement therapy; laronidase; α-L-iduronidase