TUMOR-NECROSIS-FACTOR-ALPHA AND X-LINKED ADRENOLEUKODYSTROPHY

The two most common forms of X-linked adrenoleukodystrophy (X-ALD), th e childhood cerebral form (CCER) and the adult form, adrenomyeloneurop athy (AMN), arise from the same mutations in the X-ALD gene at Xq28. T hese two forms are distinguished by the degree of cerebral inflammatio n. Segregation analysis suggests that an autosomal modifying gene may be a major determinant of phenotype in X-ALD. Thus, a modifying gene c ould be involved in initiating or promoting the inflammatory response. In this study we detected a difference in tumor necrosis factor-alpha (TNF-alpha) bioactivity, but not TNF-alpha protein levels, in serum f rom some advanced CCER patients. Early-stage CCER patients and AMN pat ients were in the normal range. Allelic differences in TNF-alpha or le vels of soluble TNF receptor did not account for bioactivity differenc es or phenotypic heterogeneity in X-ALD.