[Adult-onset hereditary leukoencephalopathy: classification and molecular basis of the disorder].

[alexander disease]

Adult-onset leukoencephalopathy involving the white matter of the brain is a heterogeneous disorder that exhibits a wide range of clinical manifestations . Recent advances in molecular genetics enable gene -based diagnosis of some forms of adult-onset leukoencephalopathy . In this review , the classification of adult-onset leukoencephalopathy based on molecular genetic findings is proposed . The autosomal dominant forms of adult-onset leukoencephalopathy include hereditary diffuse leukoencephalopathy with spheroids (HDLS ), autosomal dominant adult-onset leukoencephalopathy (ALDL ), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ), and Alexander disease . The autosomal recessive forms of adult-onset leukoencephalopathy include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL ), vanishing white matter (VWM ) with leukoencephalopathy , Nasu-Hakola disease , and metachromatic leukodystrophy (MDL ). X-chromosome-linked disorders include fragile X-associated tremor and ataxia syndrome (FXTAS ) and adrenoleukodystrophy (ALD ). Identification of the genes responsible for adult-onset leukoencephalopathy provides an important clue for elucidation of molecular pathophysiology underlying white matter disorders . One example is the identification of mutations in colony stimulating factor 1 receptor (CSF-1 R ) in patients with HDLS . Missense and splice site mutations have been found in the tyrosine kinase domain of CSF-1 R . CSF-1 R is highly expressed in microglia in the brain . It has been demonstrated that mice depleted of CSF-1 R exhibit loss of microglia in the brain . In addition , stimulation of IL -34 , a ligand of CSF-1 R , induces proliferation and activation of microglia . These findings raise an intriguing possibility that dysfunction of microglia may play a role in the pathogenesis of white matter lesions occurring in patients with HDLS .

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Diseases presenting "white matter disorders" symptom

alexander disease

canavan disease

pyruvate dehydrogenase deficiency

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