Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomyeloneuropathy is a late type of adrenoleukodystrophy. It is a hereditary disease linked to chromosome X and it is caused by abnormalities in the function of peroxisomes. Adrenomyeloneuropathy results from mutations in ABCD1 gene, that resides on chromosome Xq28 and encodes an integral peroxisomal membrane protein ALDP that belongs to the ATP-binding cassette-transporter family. The enzymatic defect concerns a transporter protein for acyl-CoA synthetase, taking part in beta-oxidation of very long chain fatty acids. This results in their accumulation in various organs. In the clinical picture spastic paresis of lower limbs, cerebellar ataxia, sensation and sphincteral disturbances predominate. This can lead to a misdiagnosis, especially shortly after the onset of symptoms, namely multiple sclerosis may be wrongly diagnosed. Coexisting endocrinological and quite often psychiatric disorders together with characteristic MRI findings facilitate the diagnosis. The diagnosis can be confirmed by a biochemical assay of very long chain fatty acids. We present a case of a 31-year-old man with adrenomyeloneuropathy. We based our diagnosis on a clinical picture and wide range of diagnostic procedures including: neuroradiologic findings, electrophysiologic, hormonal and biochemical tests, which are discussed in this article.
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PMID:[Adrenomyeloneuropathy: a late type of adrenoleukodystrophy linked to chromosome X]. 1530 8

X-linked adrenoleukodystrophy (X-ALD; OMIM #300100) is caused by defects of the ABCD1 gene on chromosome Xq28, resulting in an impairment of peroxisomal beta-oxidation and the accumulation of saturated very long chain fatty acids (VLCFAs). Primary manifestations occur in the CNS, the adrenal cortex and the testes' Leydig cells. The clinical presentation shows a marked variability which is not explained by the different X-ALD genotypes. Phenotypes range from rapidly progressive cerebral disease with childhood (childhood cerebral ALD [CCALD]) or adulthood (adult cerebral ALD [ACALD]) onset leading to death within a few years, over adult-onset adrenomyeloneuropathy (AMN) with or without focal CNS demyelination, AMN converting into a rapidly progressive, cerebral demyelinating phenotype resembling CCALD, to slow disease progression over decades, or adrenal insufficiency only. Approximately 50% of female heterozygotes develop moderate spastic paresis resembling the AMN phenotype. This review focuses on current experiences with different therapeutic approaches. Lorenzo's oil did not prove to be effective in cerebral inflammatory disease variants, but asymptomatic patients, and speculatively AMN variants without cerebral involvement, as well as female carriers may benefit from early intake of oleic and erucic acids in addition to VLCFA restriction. Hormone-replacement therapy is necessary in all patients with adrenal insufficiency. Hematopoietic stem cell transplantation has been reported to be effective in presymptomatic or early symptomatic CCALD, and may well also be a final therapeutic option in early ACALD patients. Early detection of mutation carriers and timely initiation of therapy is important for the effectiveness of all therapeutic efforts. Gene therapy of endogenous hematopoietic stem cells, pharmacological upregulation of other genes encoding proteins involved in peroxisomal beta-oxidation, reduction of oxidative stress, and possibly lovastatin are candidates for future X-ALD therapies.
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PMID:Therapy of X-linked adrenoleukodystrophy. 1875 49