Alexander disease
Encyclopedia
Alexander disease is a slowly progressing and fatal neurodegenerative disease. It is a very rare disorder which results from a genetic mutation and mostly affects infants and children, causing developmental delay and changes in physical characteristics.
), seizures, spasticity
, in some cases also hydrocephalus
, dementia
.
). It is caused by mutations in the gene
for glial fibrillary acidic protein
(GFAP) that maps to chromosome 17
q21. The mutation is not carried by the parents, rather the mutation occurs de novo
in the parental gametes that then develop into a child with Alexander disease.
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 fiber
s. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer
. The Rosenthal fibers found in Alexander disease are not distributed in the same areas or as concentrated when compared to other diseases and disorders.
CT
shows:
Categories: Start-Class medicine articlesLow-importance medicine articlesStart-Class medical genetics articlesUnknown-importance medical genetics articlesMedical genetics task force articlesStart-Class neurology articlesMid-importance neurology articlesNeurology task force articles
The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein
.
for the known cause of Alexander disease. A rough diagnosis may also be made through revealing of clinical symptoms including, enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.
, 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 and spasticity
predominate. Symptoms of the adult form may also resemble multiple sclerosis
.
There are no more than 500 reported cases.
has been attempted on a child, but did not cause the patient's condition to improve.
Clinical features
Delays in development of some physical, psychological and behavioral skills, progressive enlargement of the head (macrocephalyMacrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
), seizures, spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
, in some cases also hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
, dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
.
Pathology
Alexander disease is a genetic disorder affecting the central nervous system (midbrain and cerebellumCerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
). It is caused by mutations in the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for glial fibrillary acidic protein
Glial fibrillary acidic protein
Glial fibrillary acidic protein is an intermediate filament protein that was thought to be specific for astrocytes in the central nervous system . Later, it was shown that GFAP is also expressed by other cell types in CNS, including ependymal cells...
(GFAP) that maps to chromosome 17
Chromosome 17 (human)
125px|rightChromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 81 million base pairs and represents between 2.5 and 3 % of the total DNA in cells.Identifying genes on each chromosome is an active area of...
q21. The mutation is not carried by the parents, rather the mutation occurs de novo
De novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
in the parental gametes that then develop into a child with Alexander disease.
Alexander disease belongs to leukodystrophies, a group of diseases which affect growth or development of the myelin sheath. The destruction of white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
is accompanied by the formation of fibrous, eosinophilic
Eosinophilic
Eosinophilic refers to the staining of certain tissues, cells, or organelles after they have been washed with eosin, a dye.Eosin is an acidic dye; thus, the structure being stained is basic....
deposits known as Rosenthal fiber
Rosenthal fiber
A Rosenthal fiber is a thick, elongated, worm-like or "corkscrew" eosinophilic bundle that is found on H&E staining of the brain in the presence of long standing gliosis, occasional tumors, and some metabolic disorders.-Associated conditions:...
s. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The Rosenthal fibers found in Alexander disease are not distributed in the same areas or as concentrated when compared to other diseases and disorders.
CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
shows:
- decreased density of white matterWhite matterWhite matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
- frontal lobeFrontal lobeThe frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
predominance - +/- dilated lateral ventriclesLateral ventriclesThe lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....
Cause
Slowly by stripping the myelin sheath (a protective sheath on your nerves in your brain) the affected person would slowly begin to lose body function and eventually will not be able to talk. There is a over load of long chain fatty acids that ones body cannot dispose of. This does not follow the basic unit of life. (Everything one takes in must be able to be disposed of as waste) This over load of fatty acids will build up in your brain and that is what strips the Myelin Sheath.Categories: Start-Class medicine articlesLow-importance medicine articlesStart-Class medical genetics articlesUnknown-importance medical genetics articlesMedical genetics task force articlesStart-Class neurology articlesMid-importance neurology articlesNeurology task force articles
The cause of Alexander disease is a mutation in the gene encoding glial fibrillary acidic protein
Glial fibrillary acidic protein
Glial fibrillary acidic protein is an intermediate filament protein that was thought to be specific for astrocytes in the central nervous system . Later, it was shown that GFAP is also expressed by other cell types in CNS, including ependymal cells...
.
Diagnosis
It is possible to detect the signs of Alexander disease with Magnetic Resonance Imaging, which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MR imaging. Alexander disease may also be revealed by genetic testingGenetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
for the known cause of Alexander disease. A rough diagnosis may also be made through revealing of clinical symptoms including, enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.
Occurrence and prevalence
Its occurrence is very rare. The infantile form (63% 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 (24% 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, megalencephalyMegalencephaly
Megalencephaly is a condition in which there is an abnormally large brain. It is usually functioning abnormally. Megalencephaly is, by definition, when the brain weight is greater than average for the age and sex of the infant or child...
, developmental delay, and spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
predominate. Symptoms of the adult form may also resemble multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.
There are no more than 500 reported cases.
Treatment
There is currently no cure, or standard procedure taken for treatment. A bone marrow transplantBone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
has been attempted on a child, but did not cause the patient's condition to improve.
Prognosis
The prognosis is generally poor. With early onset, death usually occurs within 10 years after the onset of symptoms. Usually, the later the disease occurs, the slower its course is.See also
- The Myelin ProjectThe Myelin ProjectThe Myelin Project is an international scientific research organization aimed at accelerating clinical and translational research focused on myelin repair and to regenerate the nerve's myelin sheath, — a process called remyelination — destroyed in a host of diseases such as multiple...
- The Stennis FoundationThe Stennis FoundationThe Stennis Foundation is a registered nonprofit organization based in the U.S. The Foundation is primarily a fundraising organization, raising money, and then sending it to various research projects...
- Glial fibrillary acidic proteinGlial fibrillary acidic proteinGlial fibrillary acidic protein is an intermediate filament protein that was thought to be specific for astrocytes in the central nervous system . Later, it was shown that GFAP is also expressed by other cell types in CNS, including ependymal cells...
External Links
- GeneReviews/NCBI/NIH/UW entry on Alexander disease
- OMIM entries on Alexander disease
- http://www.myalexanderdisease.com