Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
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Alexander disease is a rare disorder of the central nervous system of unknown etiology. Infants with Alexander disease develop a leukoencephalopathy with macrocephaly, seizures and psychomotor retardation, leading to death usually within the first decade; patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. The pathological hallmark of all forms of Alexander disease is the presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes that contain the intermediate filament protein GFAP in association with small heat-shock proteins. We previously found that overexpression of human GFAP in astrocytes of transgenic mice is fatal and accompanied by the presence of inclusion bodies indistinguishable from human Rosenthal fibers. These results suggested that a primary alteration in GFAP may be responsible for Alexander disease. Sequence analysis of DNA samples from patients representing different Alexander disease phenotypes revealed that most cases are associated with non-conservative mutations in the coding region of GFAP. Alexander disease therefore represents the first example of a primary genetic disorder of astrocytes, one of the major cell types in the vertebrate CNS.
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PMID:Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. 1113 88

Alexander disease (AD) is a rare leukodystrophy of the central nervous system of unknown etiology. AD is characterized by progressive failure of central myelination and the accumulation of Rosenthal fibers in astrocytes, and is inevitably lethal in nature. Symptomatically, AD is associated with leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in infants, and usually leads to death within the first decade. Its characteristic magnetic resonance imaging (MRI) findings have been described as demyelination predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene, coding for glial fibrillary acidic protein (GFAP), a principal astrocytic intermediate filament protein, have been shown to lead to AD. The disease can now be detected by genetic diagnosis. We report the Korean case of an 8-month-old male patient with AD. He was clinically characterized due to the presence of psychomotor retardation, megalencephaly, spasticity, and recurrent seizures including infantile spasms which is a remarkable presentation. Demyelination in the frontal lobe and in a portion of the temporal lobe was demonstrated by brain MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L mutation in the GFAP gene, involving the replacement of guanine with thymine.
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PMID:A case of infantile Alexander disease accompanied by infantile spasms diagnosed by DNA analysis. 1704 38