Alexander Disease: Symptoms, Types, Treatment

Ian C. Langtree - Writer/Editor for Disabled World (DW)
Published: 2009/04/01 - Updated: 2023/01/28
Topic: Neurological Disorders - Publications List

Page Content: Synopsis - Introduction - Main

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. The 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.

Defining Alexander Disease

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.

Introduction

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.

Main Item

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 was born and grew up in Australia. Since then, he has traveled and lived in numerous locations and currently resides in Montreal, Canada. Ian is the founder, a writer, and editor in chief for Disabled World. Ian believes in the Social Model of Disability, a belief developed by disabled people in the 1970s. The social model changes the focus away from people's impairments and towards removing barriers that disabled people face daily. To learn more about Ian's background, expertise, and achievements, check out his bio.