Functional Studies in Adrenomyeloneuropathy

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Adrenoleukodystrophy is a genetic disorder that results from a defect in peroxisomal beta oxidation with the accumulation of saturated very long chain fatty acids (VLCFA) due to mutations in ABCD 1, a gene located at Xq28. It affects primarily the nervous system, adrenal cortex, and the Leydig cells of the testes. The phenotypic variability is high with the disparate childhood form of the disease and an adult form, adrenomyeloneuropathy (ALVIN) accounting for 80% of all cases. In affected men, AMN presents most commonly in the late twenties as a spastic paraparesis that is progressive over decades and often leads to severe disability in the fourth or fifth decades. Approximately half of the women heterozygous for ALD develop an AMN-like myelopathy in later years. AMN involves the spinal cord mainly and neuropathological studies have shown a distal axonopathy that involves most severely the ascending dorsal columns in the cervical regions and the descending corticospinal tracts. The evaluation of the therapy of AMN has been hampered by its slow rate of progression and the lack of sensitivity of currently available instruments to assess the degree of involvement. With current clinical techniques, five or more years are required to assess the effects of therapy. Using recently developed and implemented studies, preliminary data suggest that these will permit accurate assessment of disease progression in a timely fashion. These techniques are: 1) a series of quantitative tests of sensory and motor function conducted by Dr. Amy Bastian in the Motion Analysis laboratory at the Kennedy Krieger Institute, and 2): Magnetization Transfer Profile Imaging techniques of the cervical spinal tracts developed in the FM Kirby Research Center. This study proposes to examine the functional and imaging techniques in 30 patients with early adult disease secondary to ALD at baseline, 6 months, and one year to determine the specific progression in sensory and motor function and correlate those findings with the cervical cord imaging of the dorsal columns and lateral corticospinal tracts.