Adrenomyeloneuropathy Presenting as Addison's Disease in Childhood

Adrenoleukodystrophy, a sex-linked peroxisomal disorder that results in the impaired oxidation of long-chain saturated fatty acids and causes neurologic impairment, is a rare cause of Addison's disease in children. Adrenomyeloneuropathy is the name given to a biochemically identical but milder and more slowly progressive variant of adrenoleukodystrophy that affects young adults, in whom adrenal insufficiency may long precede nervous system dysfunction. The transmission of adrenomyeloneuropathy, like that of most cases of adrenoleukodystrophy, is sex-linked. Because of a preponderance of male patients among a group of patients with the onset of adrenal failure in childhood, we questioned whether this condition might be the initial manifestation of adrenomyeloneuropathy. We therefore measured the plasma concentrations of very-long-chain saturated fatty acids in eight patients with adrenal insufficiency; of these, five had elevated plasma hexacosanoic acid concentrations (range, 2.42 to 6.43 μmol per liter; mean normal level [±SD], 0.83±0.45), confirming the presence of adrenomyeloneuropathy. Magnetic resonance imaging showed clear evidence of brain involvement in all five patients. Reexploration of the family histories revealed additional missed cases. We conclude that the possibility of adrenomyeloneuropathy should be considered in any boy with Addison's disease. (N Engl J Med 1990; 322:13–6.) THE most common cause of Addison's disease (primary adrenal failure) is autoimmune adrenal disease. In adults, metastatic tumors, amyloidosis, and tuberculosis and other infectious processes account for most of the remaining cases. In children, adrenoleukodystrophy is an additional, genetically determined, rare cause of Addison's disease. 1 One form of adrenoleukodystrophy in infants is transmitted as an autosomal recessive trait; the disorder in older patients is sex-linked. 2 , 3 The basic defect in adrenoleukodystrophy is one of peroxisomal dysfunction, which results in the impaired oxidation of very-long-chain saturated fatty acids, particularly hexacosanoic acid (C26:0). 3 , 4 The accumulation of these fatty acids in the brain, adrenal . . .