title: Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison's disease improves survival and neurological outcomes.
abstract: Approximately one third of boys with X-linked adrenoleukodystophy (X-ALD) develop an acute, progressive inflammatory process of the central nervous system, resulting in rapid neurologic deterioration and death. Hematopoietic cell transplantation (HCT) can halt the progression of neurologic disease if performed early in the course of the cerebral form of X-ALD. We describe a retrospective cohort study of 90 boys with X-ALD evaluated at our institution between 2000 and 2009, to determine if early diagnosis of X-ALD following the diagnosis of unexplained adrenal insufficiency (AI) improves outcomes. We describe seven cases with a delay in the diagnosis of X-ALD and compare their outcomes to ten controls with the diagnosis of ALD made within 12 months following diagnosis of AI. At the time of evaluation for HCT, boys with a delay in the diagnosis of X-ALD had more extensive cerebral involvement and more limited functioning. These boys also were 3.9 times more likely to die and had significant advancement of cerebral disease after HCT, compared with boys with a timely diagnosis of X-ALD. In conclusion, the early diagnosis of cerebral X-ALD following the diagnosis of unexplained AI, and subsequent treatment with HCT improves both neurological outcomes and survival in boys with cerebral X-ALD.
authors.affiliation: Department of Pediatrics, University of Minnesota, 516 Delaware St. S.E., PWB 13-124, MMC 8404, Minneapolis, MN 55455, USA.
authors.forename: Lynda E
authors.initials: LE
authors.lastname: Polgreen
authors.forename: Saydi
authors.initials: S
authors.lastname: Chahla
authors.forename: Weston
authors.initials: W
authors.lastname: Miller
authors.forename: Steven
authors.initials: S
authors.lastname: Rothman
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Teresa
authors.initials: T
authors.lastname: Kivisto
authors.forename: David
authors.initials: D
authors.lastname: Nascene
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
mesh_terms: D000224:Addison Disease / Q000209:etiology*; D000309:Adrenal Insufficiency / Q000209:etiology; D000326:Adrenoleukodystrophy / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D057210:Delayed Diagnosis; D018450:Disease Progression; D042241:Early Diagnosis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome