Adrenal Insufficiency Due To X-Linked Adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder, involving mainly the white matter and axons of the central nervous system, the adrenal cortex, and the testis and a frequent but under-recognized cause of primary adrenocortical insufficiency. X-ALD is caused by a defect in the gene ABCD1 that maps to Xq 28 locus. The primary biochemical disorder is the accumulation of saturated very long chain fatty acids (VLCFA) secondary to peroxisomal dysfunction. The incidence in males is estimated to be 1:21,000 and in females 1:14,000, without any difference in the prevalence among different ethnicities. At least six distinct phenotypes have been described that differ in the age and severity of clinical presentation; however, there is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. When suspected, the diagnosis is established biochemically and prenatal testing is possible in affected families. Currently, there is no satisfying treatment to prevent the onset or modify the progression of the chronic myelopathy of X-ALD. The administration of a mixture of glyceryl-trioleate and glyceryl- trierucate, also referred as Lorenzo's Oil, has been shown to prevent disease progression in asymptomatic patients with cerebral involvement of X-ALD. Allogeneic hematopoietic stem cell (HSC) transplantation is the treatment of choice for individuals with early stages of the cerebral form of the disease. An alternative option for patients without HLA-matched donors is autologous HSC-gene therapy with lentivirally corrected cells. Once adrenal insufficiency is present, hormonal replacement therapy is identical to that of autoimmune Addison’s disease. For complete coverage of this area and all of Endocrinology, visit www.endotext.org.