Adreno-leukodystrophy (adreno-testiculo-leukomyelo-neuropathic-complex).

We have learned much about adreno-leukodystrophy (ALD) since the first case report by Siemerling and Creutzfeld [1923]. Many aspects of this disease, however, are still enigmatic and worthy of investigation (see Pathogenesis). We now realize that ALD is a constellation of clinical and pathologic presentations, all of which presumably are caused by an X-linked genetic defect in the handling of fatty acids [Migeon et al. 1981, Ogino and Suzuki 1981, Singh et al. 1984]. At the present time, and for the sake of this discussion, adreno-leukodystrophy is subdivided into 5 major clinical types: classical, X-linked juvenile ALD; X-linked adult ALD; adrenomyeloneuropathic variant (AMN); female ALD; and neonatal ALD. A sixth type, which has only pathologic and pathogenetic relevance, is the fetal form [Powers et al. 1982]. Patients may have clinical or subclinical involvement of only one organ system (e.g., adrenal) or they may have any combination of adrenal, testis, brain, spinal cord, and peripheral nerve disease [O'Neill et al. 1981]. The most common type is the classical juvenile form, followed by the AMN variant. X-linked adult ALD is uncommen and female ALD is rare. The precise nosologic placement of the neonatal form is still debated and will be discussed more fully below. Although satisfactory treatment of central nervous system demyelination in ALD and system degeneration in AMN awaits a better understanding of their pathogenesis, we are now able to control this disease complex by carrier identification and genetic counseling or by in utero detection and therapeutic abortion [Moser et al. 1984].