Early Diagnosis of Cerebral X-linked Adrenoleukodystrophy in Boys with Addison’s Disease Improves Survival and Neurological Outcomes

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 7 cases with a delay in the diagnosis of X-ALD, and compare their outcomes to 10 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 to boys with a timely diagnosis of X-ALD. Conclusion—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. Keywords adrenoleukodystrophy; adrenal insufficiency; Addison’s disease; hematopoietic cell transplantatio