Early onset Alexander disease: a case report with evidence for manifestation of the disorder in neurohypophyseal pituicytes
Abstract
We report the first case of Alexander disease diagnosed and published in the region of former Czechoslovakia. The case was characterized by early (late infantile) onset, the absence of megacephaly but with extensive internal hydrocephaly, despite a patent aqueduct.
Neuropathology revealed severe depletion of oligodendroglia and myelin, loss of axons, prominent astrocytosis with massive intracellular, dense globular GFAP aggregates which differed from typical Rosenthal fibers. Additionally, many large aggregates of GFAP were located extracellularly.
Globular GFAP aggregates were also identified in neurohypophyseal pituicytes. DNA analysis disclosed a heterozygous mutation c. 1117G>A in the GFAP, which is predicted to lead to the amino acid exchange p.Glu-373Lys (E373K) in the C-terminal tail of the GFAP protein.
The parents and a healthy sister did not show any variation in GFAP in somatic cells.