title: Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.
abstract: The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease.
authors.affiliation: Neurology Department, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Xuqin
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Gill
authors.affiliation: The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Shaw
authors.affiliation: The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Ouvrier
authors.affiliation: The Children's Hospital at Westmead, Sydney, New South Wales, Australia christopher.troedson@health.nsw.gov.au.
authors.forename: Christopher
authors.initials: C
authors.lastname: Troedson
mesh_terms: D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D035781:Siblings; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
keywords: juvenile; metachromatic leukodystrophy; onset; outcome; umbilical cord blood transplantation