Publication: Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological study
Authors
Cabrera Galván, Juan José ; Martínez Martin, María Soledad ; Déniz García, Daniel ; Araujo Ruano, Eduardo ; Travieso Aja, María del Mar
item.page.secondaryauthor
item.page.director
Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
publication.page.editor
publication.page.department
Description
Abstract
The various forms of Alexander disease
(AD) have been linked to heterozygous point mutations
in the coding region of the Human glial fibrillary acidic
protein (GFAP) gene. The aim of this study was to
confirm and characterise an adult variant of AD based
on the presence of Rosenthal fibres, which were
identified at brain autopsy.
We performed histological and immunohistochemical studies and mutation screening by cycle
sequencing of exons 1, 4, 6, and 8. A heterozygous
D128N GFAP mutation, previously described in three
other cases of adult-onset AD (AOAD), was genetically
confirmed. The mutation was seemingly sporadic.
Symptoms of the female, 65-year-old patient started with
occasionally asymmetric motor impairment and
concluded, 23 months later, with a lack of spontaneous
movement in all four limbs, reduced consciousness, an
acute respiratory problem, and eventually lethal exitus.
The most striking characteristics were a cerebellar
syndrome with subsequent clinical signs due to
brainstem and spinal cord involvement. The final
diagnosis was based on a complete autopsy, detection of
Rosenthal fibres, GFAP, vimentin, alpha B-crystallin,
ubiquitin, hsp27, neurofilament, and synaptophysin, and
the identification of the corresponding GFAP gene
mutation. Blood analyses were positive for ANA and
rheumatoid factor.
In conclusion, this work describes sporadic, rapidly
advancing AOAD in a female patient and links it with
other published cases with the same mutation.
Reflections are provided on the influence of vasculitis
and ANA in AD as well as the presence of Rosenthal
fibres in the neurohypophysis.
publication.page.subject
Citation
item.page.embargo
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. Licencia Creative Commons