Alexander Disease: Symptoms, Types, Treatment

Author: Ian C. Langtree - View Credentials
Published: 1 Apr 2009 - Updated: 28 Jan 2023

Table of Contents:
Synopsis - Definition - Overview - Related Content

Synopsis

Alexander disease is one of a group of neurological conditions known as leukodystrophies disorders, the result of abnormalities in myelin, the white matter that protects nerve fibers in the brain.

Topic Definition

Alexander Disease

Alternate names: Alexander Syndrome, Dysmyelogenic Leukodystrophy, Dysmyelogenic Leukodystrophy-Megalobare, Fribrinoid Degeneration of Astrocytes-Infantile type, Fibrinoid Leukodystrophy-Infantile type, Hyaline Panneuropathy, Leukodystrophy with Rosenthal Fibers, Megalencephaly with Hyaline Inclusion, Megalencephaly with Hyaline Panneuropathy

Alexander disease (AD) is a neurological genetic disorder that affects the brain and spinal cord. It is one of a group of conditions called leukodystrophies, genetic disorders that affect parts of the nervous system called white matter. White matter consists of cells surrounded by a protective coating called myelin. Myelin aids in the transmission of signals between nerve cells and protects the cells from damage. Alexander's disease is caused by mutations in the glial fibrillary acidic protein (GFAP) gene that maps to chromosome 17q21. It is inherited in an autosomal dominant manner, such that the child of a parent with the disease has a 50% chance of inheriting the condition if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.

Overview

Alexander disease (ALX) is a progressive and usually fatal disease. The destruction of white matter is accompanied by the formation of Rosenthal fibers, which are abnormal clumps of protein that accumulate in non-neuronal cells of the brain called astrocytes. Rosenthal fibers are sometimes found in other disorders but not in the same amount or area of the brain that is featured in ALX.

The U.S. Social Security Administration (SSA) has included Alexander Disease (ALX) - Neonatal and Infantile as a Compassionate Allowance to expedite a disability claim.

The disease occurs in both males and females, and no ethnic, racial, geographic, or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease.

Types of Alexander Disease

• Type I. This form of the disease occurs in children under the age of four and is the more severe type of AD.
• Type II. This form of the disease occurs in people over the age of four, including adults. Symptoms in this type are often less severe than those of Type I.

Infantile form is the most common type of ALX. It has an onset during the first two years of life. Usually, there are both mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution.

Symptoms of Alexander Disease

Symptoms of Type I Alexander disease include:

• Seizures
• Vomiting
• Coughing
• Slow growth
• Enlarged head
• Delays in motor development
• Delays in intellectual development
• Difficulties swallowing or breathing
• Muscle stiffness and impaired movement (spasticity)

Symptoms of Type II Alexander disease include:

• Vomiting
• Speech difficulties
• Swallowing difficulty
• Poor coordination or balance
• Abnormal spine development

Diagnosing Alexander Disease

A diagnosis of Alexander disease is usually based on radiologic studies, including MRI, CT scan, or Ultrasound. An MRI of an individual with the infantile form typically reveals white matter loss that involves the frontal lobes of the brain, abnormalities of the basal ganglia and thalamus, and possibly, enlargement of the ventricles.

Genetic testing is accomplished by looking for known or detectable mutations in the GFAP gene. In up to 94% of cases of ALX, a GFAP mutation is found. Prenatal diagnosis for couples with an affected child can be performed when the mutation responsible for ALX is known. The DNA of a fetus can be tested using cells obtained from chorionic villus sampling (CVS) or amniocentesis.

Before discovering the gene responsible for the disease, diagnosis of ALX was made by demonstrating Rosenthal fibers in a biopsy or autopsy sample from the brain. Though genetic testing has largely replaced these histologic studies, a brain biopsy or autopsy may be indicated in select cases if the diagnosis cannot be made through other means.

Treatment

There is no cure for ALX nor a standard course of treatment.

Treatment of ALX is symptomatic and supportive, primarily consisting of attention to general care and nutritional needs, antibiotic therapy for infections, and management of associated complications such as anti-epileptic drug therapy for seizures. Surgical interventions may also be required, including placing a tube and shunting for hydrocephalus.

The prognosis for ALX is generally poor. Most children with the infantile form do not survive past the age of 6.

Author Credentials: Ian C. Langtree is a writer, editor, and the founder and Editor-in-Chief of Disabled World, which he established in 2004 as one of the longest-running independent resources for disability news and information. Over more than two decades, he has written and edited thousands of articles on disability rights, health, accessibility, and assistive technology. Drawing on a global perspective shaped by extensive travel and lived experience, Ian is a committed advocate of the Social Model of Disability, the framework developed by disabled activists in the 1970s that focuses on removing societal barriers rather than on individual impairments. His writing is grounded in that framework and in a lasting commitment to disability rights, accessibility, and social inclusion. To learn more about Ian's background, expertise, and accomplishments, visit his full biography.