caa a22 4500 469044667 CHVBK 20180323132820.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01799621 doi (NATIONALLICENCE)springer-10.1007/BF01799621 Adrenoleukodystrophy: Phenotypic variability and implications for therapy [Elektronische Daten] [H. Moser, A. Moser, K. Smith, A. Bergin, J. Borel, J. Shankroff, O. Stine, C. Merette, J. Ott, W. Krivit, E. Shapiro] Summary: X-linked adrenoleukodystrophy (ALD) is a relatively common disorder that shows a great deal of phenotypic variability. Approximately half of the patients have the rapidly progressive childhood cerebral form that is associated with an inflammatory response in brain and leads to total disability or death during the first decade. Twenty five per cent or more of the patients have adrenomyeloneuropathy (AMN), a form that progresses slowly, involves the spinal cord mainly, shows little or no inflammatory response, manifests in adulthood, and is compatible with a near-normal life span. The two forms of the disease occur frequently within the same kindreds and nuclear families. Segregation analysis based on 3862 individuals in 89 kindreds points to the existence of an autosomal modifier locus with a likelihood ratio of 20:1. In addition, we present preliminary results of three types of therapy. Two hundred and four patients have received a dietary regimen that combines the administration of oils containing mono-unsaturated fatty acids (oleic and erucic) with the restricted intake of very long-chain fatty acids. This regimen normalizes the levels of satured very long-chain fatty acids in plasma within 4 weeks. It appears to improve peripheral nerve function in patients with AMN, and a large-scale trial is in progress to determine whether it can prevent the onset of neurological involvement in patients who have the biochemical abnormality of ALD but are neurologically intact. We report early results of bone marrow transplantation in 14 patients. There is encouraging but still preliminary evidence that transplantation can arrest the progression of the disease in patients with mild neurological involvement. There is urgent need to develop methods to combat the rapid progression of the cerebral forms of the disease, which so far has resisted therapeutic intervention, including immunosuppression or the administration of immunoglobulin. SSIEM and Kluwer Academic Publishers, 1992 Moser H. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Moser A. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Smith K. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Bergin A. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Borel J. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Shankroff J. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Stine O. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut Merette C. The Departments of Psychiatry and Genetics and Development, Columbia University, USA aut Ott J. The Departments of Psychiatry and Genetics and Development, Columbia University, USA aut Krivit W. Departments of Pediatrics and Neurology, University of Minnesota, USA aut Shapiro E. Departments of Pediatrics and Neurology, University of Minnesota, USA aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 645-664 0141-8955 15:4<645 1992 15 10545 https://doi.org/10.1007/BF01799621 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01799621 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moser H. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Moser A. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Smith K. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Bergin A. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Borel J. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Shankroff J. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Stine O. Kennedy Institute and Departments of Neurology, Pediatrics and Psychiatry, Johns Hopkins University, USA aut NATIONALLICENCE 700 1- Merette C. The Departments of Psychiatry and Genetics and Development, Columbia University, USA aut NATIONALLICENCE 700 1- Ott J. The Departments of Psychiatry and Genetics and Development, Columbia University, USA aut NATIONALLICENCE 700 1- Krivit W. Departments of Pediatrics and Neurology, University of Minnesota, USA aut NATIONALLICENCE 700 1- Shapiro E. Departments of Pediatrics and Neurology, University of Minnesota, USA aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 645-664 0141-8955 15:4<645 1992 15 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer