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Alexander disease

What is Alexander disease?

Alexander disease is a rare disorder of the nervous system. It is considered one of the leukodystrophies, a group of disorders in which the primary abnormality is the inability to maintain myelin. Myelin is a whitish substance that wraps around certain nerve cells and ensures the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses is disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.

Most cases of Alexander disease begin before age 2 years (the infantile form). Signs and symptoms of the infantile form typically include an enlarged brain and head (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), mental retardation, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination (ataxia).

Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers, which are found in specialized brain cells called astroglial cells. Astroglial cells support and nourish nerve cells in the brain and spinal cord.

How common is Alexander disease?

The prevalence of Alexander disease is unknown. About 500 cases have been reported since the disorder was first described in 1949.

What genes are related to Alexander disease?

Mutations in the GFAP gene cause Alexander disease.

The GFAP gene provides instructions for making a protein called glial fibrillary acidic protein. Several molecules of this protein bind together to form intermediate filaments. Intermediate filaments are important for the normal activities of astroglial cells. Mutations in the GFAP gene alter the structure of glial fibrillary acidic protein. The altered protein probably disturbs the formation of normal intermediate filaments. As a result, glial fibrillary acidic protein may accumulate as a component of Rosenthal fibers and interfere with the normal activities of astroglial cells. It is not well understood how impaired astroglial cells contribute to the abnormal formation or maintenance of myelin.

How do people inherit Alexander disease?

Alexander disease is considered an autosomal dominant disorder, which means one copy of the altered gene in each cell is sufficient to cause the disease. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In some rare adult cases, a GFAP mutation may be passed to children of an affected parent.

Alexander Disease on Wikipedia

'''Alexander disease''' is a slowly progressing fatal neurodegenerative disease.

Synonyms

* Dysmyelogenic Leukodystrophy * Dysmyelogenic Leukodystrophy-Megalobare * Fibrinoid Degeneration of Astrocytes * Fibrinoid Leukodystrophy * Hyaline Panneuropathy * Leukodystrophy with Rosenthal Fibers * Megalencephaly with Hyaline Inclusion * Megalencephaly with Hyaline Panneuropathy

Clinical features

Delays in development of some physical, psychical and behavioral skills, progressive enlargement of the head (macrocephaly), seizures, spasticity, in some cases also hydrocephalus, dementia, clumsy movements.

Pathology

This genetically based condition, affecting the central nervous system (mid brain and cerebellum)is caused by mutations in the gene for glial fibrillary acidic protein (GFAP) that maps to chromosome 17q21. Itīs inherited in an autosomal dominant manner. Alexander disease belongs to leukodystrophies, a group of diseases which affect growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers. CT shows: * decreased density of white matter * frontal lobe predominance * +/- dilated lateral ventricles

Etiology

Unknown.

Occurrence and prevalence

Very rare, occurs mostly in males. The infantile form (80% of all cases) starts usually at the age of six months or within the first two years. The average duration of the infantile form of the illness is usually about 3 years. Onset of the juvenile form (14% of all cases) presents usually between four to ten years of age. Duration of this form is in most cases about 8 years. In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms ...   [ Read More ]


External Resources

Chronic Fatigue Syndrome and the Alexander Technique - How this century-old method of releasing harmful stress may be of benefit to a patient with this disease.

Alexander Disease - Information sheet compiled by NINDS, the National Institute of Neurological Disorders and Stroke.

MCW HealthLink - Alexander Disease - Information sheet from the Medical College of Wisconsin.

Family Village / Library / Leukodystrophy - Resources on Adrenoleukodystrophy, Alexander Disease, Canavan Disease, Krabbes Disease, Metachromatic Leukodystrophy, and Refsum's Disease.

Dylan Samuel Freeman - Dylan has a very rare neurological disorder, Alexanders disease (Leukodystrophy). His story, his progress, and photographs.

Managing Pig Health and the Treatment of Disease - Practical manual providing detailed information on pigs, hogs, swine. This 600+ page book, written by Mike Muirhead and Tom Alexander is written in an easily understandable format and is aimed at everyone involved in swine production, from the farmer to the professional. Web site gives book contents and has an order form.


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