[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 .

Diseases
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Diseases presenting "wide range" symptom

22q11.2 deletion syndrome

acute rheumatic fever

adrenomyeloneuropathy

alexander disease

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

carcinoma of the gallbladder

congenital toxoplasmosis

cowden syndrome

cystinuria

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

fabry disease

gm1 gangliosidosis

harlequin ichthyosis

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

legionellosis

neonatal adrenoleukodystrophy

oral submucous fibrosis

pendred syndrome

phenylketonuria

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

systemic capillary leak syndrome

thoracic outlet syndrome

triple a syndrome

trochlear dysplasia

well-differentiated liposarcoma

werner syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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