title: Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C.
abstract: BACKGROUND
  Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months.
  
  
  METHODS
  Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype. We clinically evaluated patients' neurological involvement, giving a score of severity ranging from 0 (best) to 3 (worst) for gait abnormalities, dystonia, dysmetria, dysarthria, and developmental delay/cognitive impairment, and from 0 to 4 for dysphagia. We calculated a mean composite severity score transforming the original scores proportionally to range from 0 to 1 to summarize the clinical picture of patients and monitor their clinical course.
  
  
  RESULTS
  We compared the results after 24 months of treatment in 23 patients showing neurological manifestations. Stabilization or improvement of all parameters was observed in the majority of patients. With the exception of developmental delay/cognitive impairment, these results persisted after 48-96 months in 41 - 55% of the patients (dystonia: 55%, dysarthria: 50%, gait abnormalities: 43%, dysmetria: 41%, respectively). After 24 months of therapy the majority of the evaluable patients (n = 20), demonstrated a stabilization or improvement in the ability to swallow four substances of different consistency (water: 65%, purée: 58%, little pasta: 60%, biscuit: 55%). These results persisted after 48-96 months in 40-50% of patients, with the exception of water swallowing. Stabilization or improvement of the composite severity score was detected in the majority (57%) of 7 patients who were treated early (within 3.5 years from onset) and rarely in patients who received treatment later.
  
  
  CONCLUSIONS
  The results of this study suggest that miglustat treatment can improve or stabilize neurological manifestations, at least for a period of time; the severity of clinical conditions at the beginning of treatment can influence the rate of disease progression. This conclusion applies particularly to patients with juvenile or adult onset of the disease.
  
  
  BACKGROUND
  EudraCT number 2006-005842-35.
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. simona.fecarotta@gmail.com.
authors.forename: Simona
authors.initials: S
authors.lastname: Fecarotta
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. alromano@unina.it.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Romano
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. roberto.dellacasa@unina.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Della Casa
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. endelgiu@unina.it.
authors.forename: Ennio
authors.initials: E
authors.lastname: Del Giudice
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. diana.bruschini@libero.it.
authors.forename: Diana
authors.initials: D
authors.lastname: Bruschini
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. giumansi@unina.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mansi
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital "Santa Maria della Misericordia", Udine, Italy. bembi.bruno@aoud.sanita.fvg.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital "Santa Maria della Misericordia", Udine, Italy. dardis.andrea@aoud.sanita.fvg.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.affiliation: Department of Pediatrics, Regional Referral Center for Inherited Metabolic Disease, University of Catania, Catania, Italy. agafiu@virgilio.it.
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.affiliation: Department of Pediatrics, Unit of Rare Diseases, Gaslini Institute, Genoa, Italy. majadirocco@ospedale-gaslini.ge.it.
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.affiliation: Unit of Child Neurology, The Foundation "Carlo Besta" Neurological Institute (IRCCS), Milan, Italy. uziel@istituto-besta.it.
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.affiliation: Unit of Child Neurology, The Foundation "Carlo Besta" Neurological Institute (IRCCS), Milan, Italy. Anna.Ardissone@istituto-besta.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Ardissone
authors.affiliation: Center of Research on Immunopathology and Rare Diseases (CMID), San Giovanni Bosco Hospital and University of Turin, Turin, Italy. dario.roccatello@unito.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.affiliation: Center of Research on Immunopathology and Rare Diseases (CMID), San Giovanni Bosco Hospital and University of Turin, Turin, Italy. mirella.alpa@virgilio.it.
authors.forename: Mirella
authors.initials: M
authors.lastname: Alpa
authors.affiliation: Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. bertini@opbg.net.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. adeledamico@hotmail.com.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. dionisi@opbg.net.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Department of Pediatric Medicine, Division of Metabolism, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. deodato@opbg.net.
authors.forename: Federica
authors.initials: F
authors.lastname: Deodato
authors.affiliation: Department of Neurosciences, Psychology Clinic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. stefania.caviglia@opbg.net.
authors.forename: Stefania
authors.initials: S
authors.lastname: Caviglia
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. federico@unisi.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. silvia.palmeri@unisi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Palmeri
authors.affiliation: Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Ancona, Italy. o.gabrielli@mercurio.it.
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.affiliation: Department of Clinical Sciences, Polytechnic University of Marche, Ospedali Riuniti, Ancona, Italy. dott.luciasantoro@gmail.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. alessandro.filla@unina.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. cinziavaleria@hotmail.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. parenti@unina.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. andria@unina.it.
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat