This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Summary: Adrenoleukodystrophy is an X-linked disorder with the gene localized to Xq28. Very-long-chain fatty acids (VLCFA) accumulate in plasma, brain, and adrenal glands. One phenotype is a cerebral form which results in rapid deterioration and death, usually between ages 5 and 14. Although VLCFA levels in plasma serve to identify abnormal genotype, VLCFA levels cannot identify the rapidly progressive and fatal cerebral form (COCALD). Bone marrow transplantation (BMT) has been effective for many children with COCALD. We have found stability after BMT for up to five years for boys transplanted relatively early in the course of the disease. However, if performed too late, the outcomes are very poor. Thus, early identification of cerebral disease in boys with the biochemical abnormality is critical for positive outcome. Initial diagnosis is currently made with MR imaging together with neuropsychological testing, a rapid deterioration of function can have already occurred; sensitive early detection of such changes that herald cerebral disease is needed. Furthermore, after BMT, MR imaging has been sensitive to functional outcomes, a biological measure is needed that reflects functional change and informs about cerebral changes after BMT. MR spectroscopy offers the possibility of meeting both those needs. Preliminary evidence from our group using the 1.5 Tesla system and other groups indicate that MRS is sensitive to abnormalities associated with ALD. Such findings suggest the enormous potential for early identification and sensitive post-treatment monitoring of COCALD MRS. We have the opportunity to measure these brain metabolites using the more powerful 4Tesla scanner in this research that will yield more precise information. This study will examine the effectiveness of the 4Tesla system in detecting changes in neurochemical profile that may herald the onset of cerebral disease in conjunction with MRI and neuropsychological testing. In addition, we will examine changes in cerebral metabolites before and after bone marrow transplantation to determine whether MRS will more sensitively reflect functional changes as reflected on neuropsychological testing than does MRI or 1.5 T MRS> Patients selected in the study will be scanned in the 4 Tesla magnet at the CMRR. Patients under 8 will be sedated and those over 8 will not be sedated unless they are delayed and unable to stay still during the procedure.
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