Case Report: Infantile Onset with Adult Presentation of Alexander disease
Kole Sedlack1, Ka Loong Au2
1University of Kansas Medical Center, 2KUMC Landon Center on Aging
Objective:

To describe a unique case of Alexander disease presenting in adulthood but retrospectively demonstrating features of infantile onset followed by a prolonged period of stability.

Background:
Alexander disease is a rare autosomal dominant leukodystrophy most often caused by heterozygous mutations in GFAP. Three forms are recognized based on age of onset: infantile, juvenile, and adult. Infantile-onset cases typically present with seizures, megalencephaly, developmental delay, and spasticity, with few surviving beyond the first decade. Juvenile and adult-onset forms have more variable courses, often characterized by bulbar/pseudobulbar and pyramidal signs, though additional features such as kyphoscoliosis and dysautonomia may occur.
Design/Methods:
N/a
Results:

We present the case of a 42-year-old man who presented with progressive autonomic dysregulation, dysphonia, and gait disturbance progressing over years. He was born six weeks prematurely and experienced bilateral tonic–clonic seizures from six months to five years of age before becoming seizure-free. During childhood, he was diagnosed with an unspecified cognitive disability, developed significant kyphosis, and exhibited spasticity with chronic scissoring gait and toe walking. He remained stable until age 40, when he developed worsening urinary and fecal retention, dysphonia, and progressive gait impairment. MRI demonstrated extensive anterior-predominant white matter T2/FLAIR hyperintensities and severe atrophy of the medulla and spinal cord. CT revealed bilateral occipital–parietal subcortical and minimal periventricular calcifications. Genetic testing identified a heterozygous pathogenic GFAP c.235C>T (p.Arg79Cys) variant, commonly reported in infantile and juvenile forms.

Conclusions:

This case expands on current knowledge by providing an example in which a patient had classic infantile symptoms followed by a period of prolonged stability with subsequent juvenile/adult-onset symptoms with marked medulla and spinal cord atrophy. Additionally, it supports rarely described features as manifestation of the disease with kyphosis and intracranial calcifications.

10.1212/WNL.0000000000215275
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