title: Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients.
abstract: BACKGROUND
  The chronic neuropathic form of Gaucher disease (GD3) is characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations and central neurological involvement. Enzyme replacement therapy (ERT) has been demonstrated to be effective in non neuropathic Gaucher disease, but long term results in patients with GD3 are still limited and contrasting. A possible role of genotype in determining the response to ERT has been hypothesised.
  
  
  METHODS
  All patients affected by GD3, treated with ERT, and followed-up in 4 different Italian centres (Udine, Catanzaro, Sassari and Florence) were included. Data on clinical conditions, laboratory values, neurological and neuropsychological examinations, radiological and electrophysiological features were collected retrospectively from clinical records.
  
  
  RESULTS
  Ten patients (6 females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I, P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions from 3 to 21years. Haematological parameters and organomegaly improved/normalised in all patients. Three patients showed severe progressive skeletal deformities. 6/10 patients were neurologically asymptomatic when they started ERT for systemic symptoms. During the follow-up, 2/6 developed an important central nervous system disease; 2/6 developed mild central symptoms; and 2/6 did not show any neurological symptom after 5, and 20years of treatment respectively, despite the presence of epileptiform abnormalities at the electroencephalogram. Overall, neurological involvement worsened over time in 6/10 patients, 3 of whom developed progressive myoclonic encephalopathy and died.
  
  
  CONCLUSIONS
  ERT improved the systemic manifestations in patients with GD3, but was not able to counteract the progression of neurological symptoms in the long term.
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy. Electronic address: sechi.annalisa@aoud.sanita.fvg.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Sechi
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Deroma
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciana
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bertin
authors.affiliation: Department of Paediatrics, University Magna Graecia, Catanzaro, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Concolino
authors.affiliation: Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Florence, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Linari
authors.affiliation: Section of Childhood and Adolescence Neuropsychiatry, Department Experimental and Clinical Medicine, University of Sassari, Sassari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Perria
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
mesh_terms: D000293:Adolescent; D000328:Adult; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000188:drug therapy* / Q000235:genetics; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase; C090568:imiglucerase
keywords: Enzyme replacement therapy; Long term follow-up; Neuronopathic Gaucher disease