Περίληψη:
Objective: To characterize Alexander disease (AxD) phenotypes and
determine correlations with age at onset (AAO) and genetic mutation. AxD
is an astrogliopathy usually characterized on MRI by leukodystrophy and
caused by glial fibrillary acidic protein (GFAP) mutations.
Methods: We present 30 new cases of AxD and reviewed 185 previously
reported cases. We conducted Wilcoxon rank sum tests to identify
variables scaling with AAO, survival analysis to identify predictors of
mortality, and chi(2) tests to assess the effects of common GFAP
mutations. Finally, we performed latent class analysis (LCA) to
statistically define AxD subtypes.
Results: LCA identified 2 classes of AxD. Type I is characterized by
early onset, seizures, macrocephaly, motor delay, encephalopathy,
failure to thrive, paroxysmal deterioration, and typical MRI features.
Type II is characterized by later onset, autonomic dysfunction, ocular
movement abnormalities, bulbar symptoms, and atypical MRI features.
Survival analysis predicted a nearly 2-fold increase in mortality among
patients with type I AxD relative to those with type II. R79 and R239
GFAP mutations were most common (16.6% and 20.3% of all cases,
respectively). These common mutations predicted distinct clinical
outcomes, with R239 predicting the most aggressive course.
Conclusions: AAO and the GFAP mutation site are important clinical
predictors in AxD, with clear correlations to defined patterns of
phenotypic expression. We propose revised AxD subtypes, type I and type
II, based on analysis of statistically defined patient groups. Neurology
(R) 2011; 77: 1287-1294
Συγγραφείς:
Prust, M.
Wang, J.
Morizono, H.
Messing, A.
Brenner, M.
and Gordon, E.
Hartka, T.
Sokohl, A.
Schiffmann, R. and
Gordish-Dressman, H.
Albin, R.
Amartino, H.
Brockman, K. and
Dinopoulos, A.
Dotti, M. T.
Fain, D.
Fernandez, R. and
Ferreira, J.
Fleming, J.
Gill, D.
Griebel, M.
Heilstedt,
H.
Kaplan, P.
Lewis, D.
Nakagawa, M.
Pedersen, R. and
Reddy, A.
Sawaishi, Y.
Schneider, M.
Sherr, E.
Takiyama,
Y.
Wakabayashi, K.
Gorospe, J. R.
Vanderver, A.
