Therapy of X-linked adrenoleukodystrophy.

[adrenomyeloneuropathy]

X-linked adrenoleukodystrophy (X-ALD ; OMIM #300100 ) is caused by defects of the ABCD 1 gene on chromosome Xq 28 , 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 .

Diseases
Validation

Diseases presenting "female heterozygotes" symptom

adrenomyeloneuropathy

pyruvate dehydrogenase deficiency

x-linked adrenoleukodystrophy

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