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Journal of Pediatric Neurology 2015; 13(03): 121-125
DOI: 10.1055/s-0035-1556830
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Alexander Disease in Israel: Megalencephaly and Leukoencephalopathy and Its Differential Diagnosis

Muhammad Mahajnah
1   Department of Pediatrics, Pediatric Neurology and Child Development Center, Hillel Yaffe Medical Center, Hadera, Israel
2   Department of Pediatrics, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
,
Muhammad Abu-Rashid
3   Department of Pediatrics, Child Neurology and Development Center, Carmel Medical Center, Haifa, Israel
,
Tally Lerman-Sagie
4   Department of Pediatric Neurology, Wolfson Medical Center, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Igor Goikhman
3   Department of Pediatrics, Child Neurology and Development Center, Carmel Medical Center, Haifa, Israel
,
Nathanel Zelnik
2   Department of Pediatrics, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
3   Department of Pediatrics, Child Neurology and Development Center, Carmel Medical Center, Haifa, Israel
› Author Affiliations
Further Information

Publication History

15 July 2014

05 November 2014

Publication Date:
07 August 2015 (online)

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Abstract

Alexander disease (AD) is a rare leukodystrophy caused by overexpression of glial fibrillary acidic protein and heat shock proteins, which accumulate in the astrocytes and appear as Rosenthal fibers. Clinically, there are three main phenotypes: infantile, juvenile, and adult forms, with a highly variable clinical course. The classical, and most common phenotype, is the infantile form, which occurs during the first 2 years of life. The diagnosis of AD is based on clinical findings and, supported by magnetic resonance imaging, should be suspected in infants with leukoencephalopathy associated with progressive megalencephaly. In this article, we report two additional patients. Their mutations were already reported; however, while one of them is a common hotspot of the severe infantile-onset phenotype, the other is uncommon and was not yet reported in early infantile-onset AD. To the best of our knowledge, these are the first cases of AD reported from Israel. AD was reported anecdotally in a few other Middle Eastern countries but, since they are usually de novo sporadic mutations, they are not affected by consanguineous marriages, and do not tend to cluster in isolated ethnic populations.

Keywords

Alexander disease - glial fibrillary acidic protein - megalencephaly - Canavan disease - megaloencephalic leukoencephalopathy
 

  • References

  • 1 Gorospe JR . Alexander disease: Available at: http://www.ncbi.nlm.nih.gov/books/NBK1172/ . Accessed April 22, 2010
    PubMed
  • 2 Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A. Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 2001; 27 (1) 117-120
    CrossrefPubMedGoogle Scholar
  • 3 Prust M, Wang J, Morizono H , et al. GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology 2011; 77 (13) 1287-1294
    CrossrefPubMedGoogle Scholar
  • 4 Ashrafi MR, Tavasoli A, Aryani O, Alizadeh H, Houshmand M. Alexander disease: report of two unrelated infantile form cases, identified by GFAP mutation analysis and review of literature; the first report from Iran. Iran J Pediatr 2013; 23 (4) 481-484
    PubMedGoogle Scholar
  • 5 Ozturk C, Tezer M, Karatoprak O, Hamzaoglu A. A rare cause of neuromuscular scoliosis: Alexander disease. Joint Bone Spine 2009; 76 (2) 195-197
    CrossrefPubMedGoogle Scholar
  • 6 Hirayama T, Fukae J, Noda K , et al. Adult-onset Alexander disease with palatal myoclonus and intraventricular tumour. Eur J Neurol 2008; 15 (2) e16-e17
    CrossrefPubMedGoogle Scholar
  • 7 van der Knaap MS, Naidu S, Breiter SN , et al. Alexander disease: diagnosis with MR imaging. AJNR Am J Neuroradiol 2001; 22 (3) 541-552
    PubMedGoogle Scholar
  • 8 Tian R, Wu X, Hagemann TL , et al. Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes. J Neuropathol Exp Neurol 2010; 69 (4) 335-345
    CrossrefPubMedGoogle Scholar
  • 9 Kaya N, Imtiaz F, Colak D , et al. Genome-wide gene expression profiling and mutation analysis of Saudi patients with Canavan disease. Genet Med 2008; 10 (9) 675-684
    CrossrefPubMedGoogle Scholar
  • 10 Elpeleg ON, Anikster Y, Barash V, Branski D, Shaag A. The frequency of the C854 mutation in the aspartoacylase gene in Ashkenazi Jews in Israel. Am J Hum Genet 1994; 55 (2) 287-288
    PubMedGoogle Scholar
  • 11 Unalp A, Altiok E, Uran N, Oztürk A, Yüksel S. Novel mutation of aspartoacylase gene in a Turkish patient with Canavan disease. J Trop Pediatr 2008; 54 (3) 208-210
    PubMedGoogle Scholar
  • 12 López-Hernández T, Ridder MC, Montolio M , et al. Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. Am J Hum Genet 2011; 88 (4) 422-432
    CrossrefPubMedGoogle Scholar
  • 13 Topçu M, Gartioux C, Ribierre F , et al. Vacuoliting megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22qtel. Am J Hum Genet 2000; 66 (2) 733-739
    CrossrefPubMedGoogle Scholar
  • 14 Mahmoud IG, Mahmoud M, Refaat M , et al. Clinical, neuroimaging, and genetic characteristics of megalencephalic leukoencephalopathy with subcortical cysts in Egyptian patients. Pediatr Neurol 2014; 50 (2) 140-148
    CrossrefPubMedGoogle Scholar
  • 15 Ben-Zeev B, Levy-Nissenbaum E, Lahat H , et al. Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in Israeli patients and a higher than expected carrier rate among Libyan Jews. Hum Genet 2002; 111 (2) 214-218
    CrossrefPubMedGoogle Scholar