title: Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.
abstract: BACKGROUND
  Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.
  
  
  METHODS
  Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.
  
  
  RESULTS
  A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.
  
  
  CONCLUSIONS
  The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population.
authors.affiliation: Centro de Genetica Medica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira/FIOCRUZ, Rio de Janeiro, RJ, Brazil. dafne@iff.fiocruz.br
authors.forename: Dafne D G
authors.initials: DD
authors.lastname: Horovitz
authors.forename: Tatiana S P C
authors.initials: TS
authors.lastname: Magalhães
authors.forename: Angelina
authors.initials: A
authors.lastname: Acosta
authors.forename: Erlane M
authors.initials: EM
authors.lastname: Ribeiro
authors.forename: Liane R
authors.initials: LR
authors.lastname: Giuliani
authors.forename: Durval B
authors.initials: DB
authors.lastname: Palhares
authors.forename: Chong A
authors.initials: CA
authors.lastname: Kim
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Paula
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kerstenestzy
authors.forename: Mara A D
authors.initials: MA
authors.lastname: Pianovski
authors.forename: Maria Ione F
authors.initials: MI
authors.lastname: Costa
authors.forename: Francisca C
authors.initials: FC
authors.lastname: Santos
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Aranda
authors.forename: Jordão
authors.initials: J
authors.lastname: Correa Neto
authors.forename: Gervina Brady Moreira
authors.initials: GB
authors.lastname: Holanda
authors.forename: Laércio
authors.initials: L
authors.lastname: Cardoso
authors.forename: Carlos A B
authors.initials: CA
authors.lastname: da Silva
authors.forename: Renata C F
authors.initials: RC
authors.lastname: Bonatti
authors.forename: Bethania F R
authors.initials: BF
authors.lastname: Ribeiro
authors.forename: Maria do Carmo S
authors.initials: Mdo C
authors.lastname: Rodrigues
authors.forename: Juan C
authors.initials: JC
authors.lastname: Llerena
mesh_terms: D002675:Child, Preschool; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase