GFAP mutations, age at onset, and clinical subtypes in Alexander disease.

[alexander disease]

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 .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 Ï‡(2 ) tests to assess the effects of common GFAP mutations . Finally , we performed latent class analysis (LCA ) to statistically define AxD subtypes .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 . R 79 and R 239 GFAP mutations were most common (16 .6 % and 20 .3 % of all cases , respectively ). These common mutations predicted distinct clinical outcomes , with R 239 predicting the most aggressive course .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 .

Diseases
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Diseases presenting "caused by glial fibrillary acidic protein" symptom

alexander disease

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