The most common variant of adrenoleukodystrophy (ALD) is an X-linked recessive disorder which involves mainly the adrenal cortex and the white matter of the CNS. Often there is a family history of maternal uncles having died of Addison’s disease or of a progressive neurological illness which was regarded at that time as Schilder’s disease. The age at onset of neurological symptoms is usually between 5 and 9 years. Features of adrenal insufficiency usually appear 1–3 years before the neurological symptoms, but sometimes they follow the symptoms of brain disorder. In some cases a definite diagnosis of Addison’s disease has been made before any neurological disorder is evident, on the basis of increased pigmentation, episodes of vomiting, and catastrophic reactions to intercurrent infections. In others, neurological deterioration may have continued for some years without endocrine symptoms, and sophisticated investigations may be needed to show evidence of adrenocortical dysfunction. The earliest neurological symptoms are often vague. Behavioral difficulties vary from withdrawn to bizarre hyperactive and aggressive behavior. Failure to make progress in learning may be evident. Months or years of psychiatric treatment may follow until deteriorating school performance and other neurological symptoms force recognition of the organic nature of the disease. A progressive dementia occurs. Disturbances of gait are caused by a spastic paraplegia. Other symptoms are clumsiness and incoordination, dysarthria, dysphagia, and decreased hearing. Decreased vision is caused by optic atrophy or bilateral cerebral occipital white matter lesions. Cerebellar ataxia may be present but is usually not prominent. Epileptic seizures are often multifocal. Signs of peripheral neuropathy are not usually a feature of the disease. In the beginning there may be an asymmetry of neurological deficits with a hemiparesis or a hemianopsia. The disease is always progressive, but the pace of deterioration is variable. In the final stage a spastic quadriplegia develops with decorticate posturing. The affected boys are blind, deaf, and mute. Death usually occurs a few years after onset.
KeywordsAdrenal Insufficiency Cholesterol Ester Myelin Sheath White Matter Lesion Cerebellar Ataxia
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