X - linked adrenoleukodystrophy (Adrenomyeloneuropathy; melanodermic leukodystrophy, Schilder disease-Addison disease; Bronze-Schilder disease; Creutzfeldt-Siemerling) (X-linked adrenoleukodystrophy) - Gen ABCD1

Adrenoleukodystrophy X-linked is a disease which mainly affects men, and is characterized by neurological manifestations and adrenal insufficiency. Individuals affected by this process, preferably male, have progressive destruction of lipids surrounding brain nerve cells and spinal cord (myelin), and adrenocortical hormone insufficiency motivated by the damage to the outer layer of the glands adrenals (adrenal cortex). Adrenal insufficiency can cause weakness, weight loss, skin changes, vomiting and coma. In addition, cells can be affected testicular Leidig. There are at least three varieties X - linked adrenoleukodystrophy: a) cerebral form; b) Adrenomyeloneuropathy; c) isolated Addison 's disease.

  • Childhood cerebral form. It is characterized because children have learning and behavioral problems that usually appear between 4 and 10 years, symptoms worsen over time. These children show problems reading, writing, comprehension of speech and writing. In addition, they may show aggressive behavior, vision problems and adrenal gland functional disorders. The progression is variable and may reach disability in several years.
  • Adrenomyeloneuropathy. It is characterized by signs and symptoms appear between the onset of adulthood and middle stage of life. Affected manifest progressive stiffness and weakness in the lower extremities (paraparesis), urinary and genital alteration, and often have some degree of brain dysfunction. Most also they have adrenocortical insufficiency. In some severely affected individuals, damage to the brain and nervous system can cause premature death.
  • Addison 's disease isolated. This variety has only signs of adrenocortical insufficiency. Individuals with this type suffer from weakness, weight loss, skin changes, vomiting, and may even coma. These people, over time, can develop any signs of X - linked adrenoleukodystrophy

The genetic basis of this process resides in mutations ABCD1 (ATP-Binding Cassette, Subfamily D [ALD] member 1) gene, belonging to the family of genes called ABC (ATP-Binding Cassette Transporters), or ATP (ATPase Superfamily ). The ABCD1 gene, located on the long arm of the X chromosome (Xq28), encoding ALDP (Adrenoleukodystrophy Protein) protein. This protein is found in the cell membrane of peroxisomes, which is part of the conveyor system coupled membrane with another molecule to form a dimer. Its function is to transport molecules into peroxisomes to be processed, such as with the oxidation of fatty acids (b-oxidation). The transport system in which the protein participates ALDP transports fatty acids long chain (VLCFAs: Very Long Chain Fatty Acids). When there ABCD1 gene mutations, the described over 650, there would be a decrease or absence of ADLP protein, and could not carry these fatty acids into peroxisomes to be degraded, which is They accumulate in the circulation and tissues, causing an alteration of the adrenal glands and brain and spinal cord myelin.

X - linked adrenoleukodystrophy has a pattern of X - linked inheritance, one of the sex chromosomes, so in males, to a single copy of this chromosome exist, the existing mutation on the X chromosome would lead to demonstrations. In women, as there are two X chromosomes, a single altered in one of two chromosomes, copy often leads to a less severe form of the disease. Signs and symptoms of X - linked adrenoleukodystrophy tend to appear at a later age in women than in men. Affected women often develop Adrenomyeloneuropathy type characteristics.

Tests in IVAMI: in IVAMI perform detection of mutations associated conadrenoleucodistrofía linked to X through the complete PCR amplification of exons ABCD1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated card with dried blood sample if postnatal diagnosis. (IVAMI can mail the card to deposit the blood sample).