Disease Directory Alexander Disease
Neurological

Alexander Disease

Also known as: AxD, GFAP mutation, fibrinoid leukodystrophy

Prevalence

1-9 per 1,000,000 (Orphanet)

Onset

Infantile, Juvenile, Adult

Type

Autosomal dominant genetic (de novo in most cases)

Gene

GFAP

About Alexander Disease

Alexander disease is a rare leukodystrophy caused by dominant gain-of-function mutations in GFAP encoding glial fibrillary acidic protein. Mutant GFAP accumulates in Rosenthal fibers within astrocytes, disrupting astrocyte function and impairing myelination. The infantile form is most severe, causing progressive macrocephaly, seizures, and developmental regression; juvenile and adult forms have more varied presentations including bulbar symptoms and autonomic dysfunction.

Common Clinical Features

Macrocephaly (infantile) Seizures Psychomotor retardation White matter abnormality on MRI Bulbar dysfunction (juvenile/adult) Palatal tremor Ataxia

Clinical Trial Eligibility Tips

What to know before applying to Alexander Disease trials.

GFAP pathogenic variant (de novo gain-of-function) confirmed by sequencing is required for trial enrollment

Brain MRI showing characteristic frontal-predominant leukoencephalopathy with periventricular rim is diagnostic

CSF GFAP level is an emerging biomarker for disease severity and treatment monitoring

Antisense oligonucleotide (ASO) trials targeting GFAP are in development — no prior ASO therapy is an exclusion criterion

Patient Resources

Patient Organization

United Leukodystrophy Foundation

Visit website ↗

Natural History Registry

Alexander Disease Registry (UNC Chapel Hill)

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:58)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Alexander Disease trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Alexander Disease. Updated daily.

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