Case report A case of infantile Alexander disease with a milder phenotype and a novel GFAP mutation, L90P Yoshiko Suzuki a, * , Naomi Kanazawa b , Junko Takenaka a , Akihisa Okumura a , Tamiko Negoro a , Seiichi Tsujino b a Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan b Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, 4-1-1 Ogawahigashi-Cho, Kodaira, Tokyo 187-8502, Japan Received 9 January 2003; received in revised form 1 July 2003; accepted 1 July 2003 Abstract Alexander disease is a leukoencephalopathy that usually presents during infancy with developmental delay, macrocephaly and seizures. Several sequencing analyses have identified mutations in the gene encoding glial fibrillary acidic protein (GFAP) of patients with Alexander disease. We described a girl who developed seizures in infancy with atypical CT findings and in whom a novel heterozygous mutation, L90P (283T ! C), was detected in exon 1 of the GFAP gene. The neurological deterioration was mild and appeared relatively late for infantile onset. q 2003 Elsevier B.V. All rights reserved. Keywords: Alexander disease; Mutation; GFAP; Infantile; Computed tomography 1. Introduction Alexander disease is an uncommon degenerative dis- order that is associated with myelin loss in a rostrocaudal gradient. The pathologic hallmark of the disorder is the presence of Rosenthal fibers located within astrocytes. Although brain biopsy or postmortem examination has been the only confirmatory test for a diagnosis, glial fibrillary acidic protein (GFAP) mutations have now been found in several cases of Alexander disease [1–7]. These mutations found in child patients are considered to be de novo and dominant. We describe a girl who had white matter abnormalities with frontal preponderance and a novel mutation within the GFAP gene. The patient had developed seizures in infancy but developmental deterioration was mild and appeared relatively late for infantile onset. 2. Case report The patient was a 5-year-old girl born as the first child of Japanese non-consanguineous parents. Her mother had a history of systemic lupus erythematosus. The rest of the family were healthy. Her prenatal and perinatal history were unremarkable. At the age of 5 months, she developed a cluster of complex partial seizures, controlled by pheno- barbitone. Macrocephaly was not present. Brain CT at 5 months of age revealed scattered high density areas in the basal ganglia (Fig. 1A), which remained the same on the latest CT scan at 4 years of age. Normal development continued until 7 months of age, motor development then slowed down, such that she could only walk with support at 12 months and without only at 21. She was referred to our hospital at 4 years 6 months of age. Her height was 90 cm (below 3rd percentile) and head circumference 50.8 cm (75th percentile). She walked clumsily and could speak simple sentences. Deep tendon reflexes and muscle tone were normal. MR imaging showed predominantly frontal involvement of the white matter with low signal intensity on T1-weighted images and high signal intensity on T2-weighted. The subcortical U-fibers were relatively spared (Fig. 1B). Lesions were also observed in the putamen, globus pallidus, caudate nucleus, medulla oblongata and dorsal pons. Proton MR spectroscopy of the frontal white matter showed reduced N-acetylaspartic acid/ creatine, increased choline/creatine ratios and accumulation of lactate, though the accumulation of lactate was not Brain & Development 26 (2004) 206–208 www.elsevier.com/locate/braindev 0387-7604/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0387-7604(03)00132-3 * Corresponding author. Tel.: þ81-52-744-2294; fax: þ 81-52-744-2974. E-mail address: ysuzuki@med.nagoya-u.ac.jp (Y. Suzuki).