J Korean Med Sci.  2006 Oct;21(5):954-957. 10.3346/jkms.2006.21.5.954.

A Case of Infantile Alexander Disease Accompanied by Infantile Spasms Diagnosed by DNA Analysis

• Lee JM
• Kim AS
• Lee SJ
• Cho SM
• Lee DS
• Choi SM
• Kim DK
• Ki CS
• Kim JW

• KMID: 1781924
• DOI: http://doi.org/10.3346/jkms.2006.21.5.954

Abstract

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.

Keyword

Alexander Disease; Spasms, Infantile; Mutation; Glial Fibrillary Acidic Protein; Magnetic Reso-nance Imaging

MeSH Terms

Spasms, Infantile/*etiology
*Mutation
Male
Magnetic Resonance Imaging
Infant
Humans
Glial Fibrillary Acidic Protein/*genetics
Electroencephalography
Alexander Disease/complications/*diagnosis

Figure

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  Fig. 1 General appearance (A) and traction response (B) of the patient at the age of 8 months on admission are compared with (C) and (D) at the age of 20 months.

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  Fig. 2 MRI reveals regions with decreased signal in the bilateral frontal white matter on T1-weighted imagies (A) and high signal intensity on T2-weighted images (B) mainly on the frontal lobe. MRI reveals regions with more decreased signal in the bilateral frontal white matter on T1-weighted imagies (C) and higher signal intensity on T2-weighted images (D) than previous MRI and decreased volume in both frontal white matter.

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  Fig. 3 Identification of the GFAP gene mutation. Direct sequencing analysis of the patient and his family members demonstrates a de novo R239L mutation due to a G to T transversion (c.716G>T; arrow) in exon 4 of the GFAP gene.

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  Fig. 4 Interictal EEG shows focal slowing on the frontal lobe mixed with fast beta waves at the age of 8 months (A). Interictal EEG shows asynchronous high voltage multifocal spikes at the age 20 months (B).

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