What is Alexander Disease?
Alexander disease (AxD) is a rare, progressive neurological disorder and form of leukodystrophy caused by changes in the GFAP (glial fibrillary acidic protein) gene.
Photo: Olivia Kay Borodychuk, 10/10/08-4/28/17, Alexander Disease
GFAP is a protein found primarily in astrocytes, cells that play an important role in supporting and protecting the brain and spinal cord. In Alexander disease, abnormal GFAP builds up within astrocytes and disrupts their normal function. This leads to progressive damage within the central nervous system, including the brain’s white matter.
A hallmark of Alexander disease is the presence of Rosenthal fibers, abnormal protein deposits that accumulate within astrocytes.
Alexander disease can begin at any age, from infancy through adulthood, and symptoms and progression can vary significantly from one person to another.
How do you get Alexander Disease?
Alexander disease is caused by a disease-causing change, or pathogenic variant, in the GFAP gene.
Alexander disease is inherited in an autosomal dominant manner. However, in most people with Alexander disease, the GFAP variant occurs for the first time in that individual and was not inherited from either parent. This is called a de novo variant.
In some families, Alexander disease is inherited from an affected parent. Because inheritance and recurrence risk can vary depending on the individual genetic findings, families should speak with a genetic counselor or Alexander disease specialist about their specific situation.
Could other children in the family also have Alexander Disease?
For most families in which the GFAP variant occurred de novo, the chance that another child will have Alexander disease is low, although it is not zero.
If a parent carries the GFAP variant, each child has a 50% chance of inheriting that variant.
Genetic testing of parents and genetic counseling can help families better understand their individual recurrence risk and options for family planning.
How is Alexander Disease diagnosed?
Alexander disease may first be suspected based on an individual’s symptoms and characteristic findings on brain MRI. Diagnosis is confirmed through genetic testing that identifies a disease-causing variant in the GFAP gene.
Because Alexander disease can present differently depending on age and the individual, evaluation by a neurologist, geneticist, or other specialist familiar with leukodystrophies can be important in reaching an accurate diagnosis and developing an appropriate care plan.
What are the different forms of Alexander Disease?
Alexander disease has historically been described as neonatal, infantile, juvenile, or adult based on the age at which symptoms begin. More recent research has shown that Alexander disease exists along a broad clinical spectrum, and age of onset alone does not always predict how the disease will affect an individual.
Other classification systems, including Type I and Type II Alexander disease, have been developed based on clinical symptoms and MRI findings.
Regardless of the classification, the symptoms, severity, and rate of progression can vary considerably from person to person. Ongoing care with clinicians experienced in Alexander disease is important throughout the lifespan.
For more information and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.
Is there treatment for Alexander Disease?
ZANVASTRO™ (zilganersen) is an FDA-approved treatment for pediatric and adult patients with Alexander disease.
Families who are interested in learning more about ZANVASTRO, including treatment information, safety information, and available patient support resources, can visit the official ZANVASTRO website from Ionis Pharmaceuticals. Learn more here.
Individuals and families should talk with their healthcare provider or an Alexander disease specialist about available treatment options and whether ZANVASTRO may be appropriate for them.
For comprehensive leukodystrophy care, families can also connect with a Leukodystrophy Care Network Center.
Ongoing Care
Even with the availability of disease-modifying treatment, comprehensive and proactive medical care remains an important part of managing Alexander disease.
Depending on an individual’s needs, care may involve specialists in neurology, rehabilitation, feeding and nutrition, gastroenterology, pulmonology, physical and occupational therapy, speech and communication, urology, sleep medicine, and other areas.
The Leukodystrophy Care Network was established to help individuals and families affected by leukodystrophies access comprehensive, specialized care.
Additional Resources for Families
Leukodystrophy Care Network
Hunter’s Hope Foundation – Family Care
Details about ZANVASTRO
Research – Children’s Hospital of Philadelphia