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
