title: Enzyme replacement therapy in two patients with an advanced severe (Hurler) phenotype of mucopolysaccharidosis I.
abstract: Although offered, two of our Hurler patients (OMIM 607014) had not undergone bone marrow transplantation at an early stage of their disease. Rapid disease progression had resulted in a range of signs and symptoms representative of advanced neurodegeneration and debilitating somatic Hurler disease. As general palliative care had only little impact on the burden of disease, laronidase (Aldurazyme) treatment was introduced in an attempt to alleviate somatic symptoms and to improve the quality of their lives. Therapeutic benefits from enzyme replacement therapy included improvements in general physical condition and mood, as well as normalisation of the sleep patterns, disappearance of sleep apnoea syndrome and reduction of hepatosplenomegaly. Improvements in the joint mobility were mainly limited to the wrists and hips. In addition, improvements in cardiac function, stool habits, visual acuity, corneal clouding and hearing were observed in one or both patients. Irreversible skeletal changes did not deteriorate. The neurological outcome of these patients is likely not influenced as laronidase is believed not to pass the blood-brain barrier. Therefore, the decision to initiate this therapy in transplant-naïve Hurler patients with an advanced stage of the disease should be taken after careful consideration.
  
  
  CONCLUSIONS
  We are of the opinion that the option of enzyme therapy should not be excluded in severely affected Hurler patients who cannot undergo bone marrow transplantation. Stabilization or amelioration of somatic disease and improvement of the quality of their lives should be embraced as therapeutic goals.
authors.affiliation: Referral Centre of the Ministry of Health and Social Welfare for Surveillance of Congenital Anomalies in the Republic of Croatia, Department of Paediatrics, Children's University Hospital Zagreb, Klaiceva 16, 10,000 Zagreb, Croatia. visnjatokic@yahoo.com
authors.forename: Visnja
authors.initials: V
authors.lastname: Tokic
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisic
authors.forename: Nevenka
authors.initials: N
authors.lastname: Huzjak
authors.forename: Giorgie
authors.initials: G
authors.lastname: Petkovic
authors.forename: Ksenija
authors.initials: K
authors.lastname: Fumic
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
mesh_terms: D005260:Female; D006801:Humans; D007068:Iduronidase / Q000378:metabolism / Q000627:therapeutic use*; D007223:Infant; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007068:Iduronidase