Adrenomyeloneuropathy
Encyclopedia
Adrenomyeloneuropathy is a rare inherited disorder. It is a milder form of X-linked adrenoleukodystrophy
(X-ALD). In adrenoleukodystrophy, young children generally exhibit cerebral dysfunction, with rapid progression to dementia and quadriparesis. Adrenomyeloneuropathy progresses more slowly, with patients first showing symptoms of weakness and spasticity in adolescence or adulthood. Patients also develop adrenal insufficiency, (Addison's Disease
). The gene responsible is located on the long arm of chromosome X, resulting in a sex link
ed pattern of expression. Males carrying any of several mutations in the gene (known as hemizygous) will always be affected, with about 50% developing X-ALD in early childhood and about 50% developing AMN as adolescents or adults. It is unknown why there is such a range in severity of expression, but forms of the disease are found in within the same affected families, (same mutation). The various forms of the disease affect 1 in 21,000 males.
This disease is caused by defective beta-oxidation of fatty acids in peroxisome
s that leads to elevated serum concentrations of very-long-chain saturated fatty acids (VLCFA) and accumulation of cholesterol esters of the fatty acids and gangliosides in the membranes of cells in the brain, adrenal cortex, and other organs. In AMN, this accumulation causes a primary adrenal insufficiency and progressive neurological dysfunction.
diagnosis of any male with adrenal insufficiency. Most patients develop symptoms of weakness, spasticity, and distal polyneuropathy and may also develop emotional lability, mania, or psychosis. Bladder dysfunction is a common manifestation of adrenomyeloneuropathy and can be a presenting symptom of this disease
s in the blood, and will also detect most female carriers, but further testing may be required to detect all female carriers). The early identification of affected males is particularly important, as Adrenal hormone replacement therapy is critical and may be life saving. If a family member tests positive, they can receive this treatment, and prevent certain life threatening symptoms, such as an Addisonian crisis.
Adrenoleukodystrophy
Adrenoleukodystrophy is a rare, inherited disorder that leads to progressive brain damage, failure of the adrenal glands and eventually death. ALD is a disease in a group of genetic disorders called leukodystrophies, whose chief feature is damage to myelin...
(X-ALD). In adrenoleukodystrophy, young children generally exhibit cerebral dysfunction, with rapid progression to dementia and quadriparesis. Adrenomyeloneuropathy progresses more slowly, with patients first showing symptoms of weakness and spasticity in adolescence or adulthood. Patients also develop adrenal insufficiency, (Addison's Disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
). The gene responsible is located on the long arm of chromosome X, resulting in a sex link
Sex Link
Sex-links are cross-bred chickens whose color at hatching is differentiated by sex, thus making chick sexing an easier process. Sex-links come in many varieties, few of which are a true breed...
ed pattern of expression. Males carrying any of several mutations in the gene (known as hemizygous) will always be affected, with about 50% developing X-ALD in early childhood and about 50% developing AMN as adolescents or adults. It is unknown why there is such a range in severity of expression, but forms of the disease are found in within the same affected families, (same mutation). The various forms of the disease affect 1 in 21,000 males.
This disease is caused by defective beta-oxidation of fatty acids in peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
s that leads to elevated serum concentrations of very-long-chain saturated fatty acids (VLCFA) and accumulation of cholesterol esters of the fatty acids and gangliosides in the membranes of cells in the brain, adrenal cortex, and other organs. In AMN, this accumulation causes a primary adrenal insufficiency and progressive neurological dysfunction.
Presentation
Adrenomyeloneuropthy begins in adolescence or adulthood. The mutation is estimated to be the cause of adrenal insufficiency in approximately 35% of patients with idiopathic Addison’s disease and should be considered in the differentialdiagnosis of any male with adrenal insufficiency. Most patients develop symptoms of weakness, spasticity, and distal polyneuropathy and may also develop emotional lability, mania, or psychosis. Bladder dysfunction is a common manifestation of adrenomyeloneuropathy and can be a presenting symptom of this disease
Relatives of an Affected Patient
After diagnosis, it is important for the patient's blood relatives to be analysed and those at risk have diagnostic blood work to determine if they have the disease. (The test checks for very long chain fatty acidVery long chain fatty acid
A very long chain fatty acid is a fatty acid with aliphatic tails longer than 22 carbons.Unlike most fatty acids, VLCFAs are too long to be metabolized in the mitochondria, and must be metabolized in peroxisomes....
s in the blood, and will also detect most female carriers, but further testing may be required to detect all female carriers). The early identification of affected males is particularly important, as Adrenal hormone replacement therapy is critical and may be life saving. If a family member tests positive, they can receive this treatment, and prevent certain life threatening symptoms, such as an Addisonian crisis.