Mouse models and genetic modifiers in X-linked adrenoleukodystrophy.

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder that affects 1 in 35000 males and is marked by neurodegeneration, adrenal insufficiency and infertility. All characteristics are not always present in every X-ALD patient and the rate of progression varies. X-ALD has a variety of phenotypes, the two major phenotypes are cerebral X-ALD (CALD) and adrenomyeloneuropathy (AMN)(Moser 2000). The Other patients only have adrenal insufficiency, or rarely, remain asymptomatic. As the nature of X-ALD is progressive, these adrenal and asymptomatic patients often develop nervous system involvement as they age. CALD most commonly presents in childhood (mean age of onset, 7.2 ±1.7 years) but can also strike adolescents and adults. There are focal sites of demyelination of the cerebral white matter associated with perivascular inflammation of the affected site. This inflammatory demyelination is rapidly progressive over the course of a few years and usually ends in early death. AMN presents in adulthood (mean age of onset, 28 ± 9 years) as a peripheral myelopathy with spinal cord involvement usually with no brain disease. There is a lack of inflammation at these sites and this disease progresses much more slowly than the cerebral form. A significant fraction of AMN patients eventually develop brain disease. Adrenal insufficiency is often, but not always, present in both cerebral and AMN patients.