Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions.
BACKGROUND
The term chorea-acanthocytosis describes a heterogeneous group of neurodegenerative disorders with variable clinical features and modes of inheritance. The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined.


OBJECTIVE
To describe features of phenotype, inheritance, and neuropathological findings in a family with this disorder.


METHODS
Clinical and hematologic evaluations were performed on all available family members and neuropathological examination was performed on one case.


RESULTS
Autosomal dominant inheritance was evident, with variable clinical features of chorea or parkinsonism, marked cognitive changes, but no seizures or peripheral neurologic abnormalities. Abnormalities of band 3 were demonstrated on gel electrophoresis of red blood cell membranes. Neuropathological examination revealed severe neuronal loss of the caudate-putamen and intranuclear inclusion bodies in many areas of the cerebral cortex. These inclusion bodies were immunoreactive for ubiquitin, expanded polyglutamine repeats, and torsinA.


CONCLUSIONS
This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats. Intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders and may provide a clue to etiopathogenesis, in addition to potentially indicating a function of torsinA.
Walker
R H
RH
Department of Neurology, Veterans Affairs Medical Center, Bronx, NY, USA. ruth.walker@mountsinai.org
Morgello
S
S
Davidoff-Feldman
B
B
Melnick
A
A
Walsh
M J
MJ
Shashidharan
P
P
Brin
M F
MF
D000050:Acanthocytes / Q000473:pathology; D000328:Adult; D001284:Atrophy; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D002819:Chorea / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry / Q000473:pathology*; D010375:Pedigree; D010455:Peptides / Q000032:analysis*
D010455:Peptides; C097188:polyglutamine