Triple A syndrome ...; Allgrove syndrome (Triple A syndrome, Allgrove syndrome) - Gen AAAS
Triple A syndrome, also known as Allgrove syndrome is an inherited process is characterized by three specific features: achalasia, Addison 's disease (primary adrenal insufficiency) and alacrimia. Although most people with triple A syndrome manifest three characteristics, some individuals only have two.
This condition begins to manifest during the first decade of life with episodes of severe hypoglycemia and is associated with neurological disorders such as motor or sensory autonomic or peripheral neuropathy, dementia, mental retardation, ataxia and dysarthria. Cases with optic atrophy, microcephaly, skin disorders (hyperkeratosis), short stature and osteoporosis are also presented.
This process is due to mutations in the AAAS gene (ADRACALA), located on the long arm of chromosome 12 (12q13). This gene encodes ALADIN ( "alacrima Achalasia Neurologic adrenal insufficiency disorder"), a protein of 546 amino acids that is part of the family of nucleoporins the nuclear pore complex (NPC) protein. Although the exact function is unknown, nucleoporins play an important role in transport processes between the nucleus and cytoplasm and may have a function ALADIN structural scaffold as it interacts with NPC.
They have been described at least 49 mutations in the gene responsible AAAS triple syndrome A. These mutations change the structure ALADIN in different ways; However, almost all mutations prevent this protein reaches its correct location on the nuclear envelope. The absence of ALADIN probably interrupts the movement of molecules through the membrane. It is believed that DNA repair proteins may be unable to enter the nucleus if ALADIN not found in the nuclear envelope. Damage to the DNA are not repaired can cause the cell to become unstable and lead to apoptosis. Although the nervous system is particularly vulnerable to DNA damage, it is not known exactly how mutations in the AAAS gene lead to signs and symptoms of triple A. syndrome Some individuals with triple A syndrome have an identified mutation in the gene AAAS. In these cases, the genetic cause of the disease is unknown.
This process is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome triple or Allgrove syndrome by complete PCR amplification of the exons of AAAS gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).