Triple A syndrome
Encyclopedia
Triple-A syndrome also known as Achalasia-Addisonianism-Alacrimia syndrome or Allgrove Syndrome, is a rare autosomal
recessive congenital disorder
. In most cases, there is no family history of it. The syndrome was discovered by Jeremy Allgrove
and colleagues in 1978. Triple A stands for achalasia-addisonianism-alacrima syndrome. Alacrima is usually the earliest manifestation. It is a progressive disorder that can take years to develop the full blown clinical picture.
(a failure of a ring of muscle fibers, such as a sphincter, to relax) of the lower esophageal sphincter
at the cardia
which delays food going to the stomach and causes dilation of the thoracic oesophagus. There may also signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate. Hypoglycemia
(low blood sugar) is often mentioned as an early sign. The disorder has also been associated with mild mental retardation
.
The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children.
gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insuffiency Neurologic disorder). In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster. Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
. In most cases, there is no family history of it. The syndrome was discovered by Jeremy Allgrove
Jeremy Allgrove
Dr. Jeremy Allgrove is consultant paediatric endocrinologist specialising in paediatric diabetes at Barts and The London NHS Trust. He is the representative of The Royal College of Paediatrics and Child Health on the Diabetes Dataset Advisory Group .Allgrove studied medicine at Corpus Christi...
and colleagues in 1978. Triple A stands for achalasia-addisonianism-alacrima syndrome. Alacrima is usually the earliest manifestation. It is a progressive disorder that can take years to develop the full blown clinical picture.
Characteristics
Individuals affected by AAA have adrenal insufficiency due to ACTH resistance, alacrima (absence of tear secretion), and achalasiaAchalasia
Achalasia , also known as esophageal achalasia, achalasia cardiae, cardiospasm, and esophageal aperistalsis, is an esophageal motility disorder involving the smooth muscle layer of the esophagus and the lower esophageal sphincter...
(a failure of a ring of muscle fibers, such as a sphincter, to relax) of the lower esophageal sphincter
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
at the cardia
Cardia
The cardia is the anatomical term for the part of the stomach attached to the esophagus. The cardia begins immediately distal to the z-line of the gastroesophageal junction, where the squamous epithelium of the esophagus gives way to the columnar epithelium of the gastrointestinal tract.Just...
which delays food going to the stomach and causes dilation of the thoracic oesophagus. There may also signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate. Hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
(low blood sugar) is often mentioned as an early sign. The disorder has also been associated with mild mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
.
The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children.
Cause and Genetics
Triple-A syndrome is associated with mutations in the AAASAAAS (gene)
Aladin also known as adracalin is a protein that in humans is encoded by the AAAS gene [achalasia, adrenocortical insufficiency, alacrimia ].- Clinical significance :...
gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insuffiency Neurologic disorder). In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster. Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.