Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triple A (Allgrove) syndrome, an autosomal recessive disease is characterized by achalasia, alacrimia and ACTH-resistant adrenal failure with progressive neurological syndrome including central, peripheral and autonomic nervous system impairment, and mild mental retardation. The triple A syndrome gene, designated AAAS, localized on chromosome 12q 13 encodes for a 546 amino acid protein called ALADIN (Alacrimia-Achlasia-Adrenal Insufficiency and Neurologic disorder). This report relates to two sisters, aged 8 and 12 years, who had vomiting, muscle weakness, alacrimia, excessive fatigue and dysphagia. Abdominal sonography, esophago-gastroduodenoscopy, barium swallow, esophageal manometry, CT scan abdomen and brain, biochemical profiles, as well as neurologic and ophthalmic evaluations were consistent with Allgrove's syndrome. Management consisted of pneumatic balloon dilatation for achalasia and initiation of cortisone therapy with successful resolution of dysphagia and other symptoms.
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PMID:AAA Syndrome, Case Report of a Rare Disease. 2949 88

Allgrove syndrome is a rare autosomal recessive syndrome of unknown prevalence. The first case of Allgrove syndrome was reported in 1978 by Allgrove. It is characterized by triad of achalasia, alacrima and adrenal hypoplasia. There are also associated autonomic and neurological manifestations. We report the case of a 7 years old boy being treated for achalasia cardia, presented with fits and altered sensorium which on further investigations was found to be due to adrenal insensitivity (Raised ACTH level, low Cortisol level, and normal Aldosterone and Renin ratio). He also had undiagnosed alacrima since birth, mild degree of hearing loss and autonomic instability in the form of episodic hypertension.
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PMID:Allgrove syndrome: case report of 7 years old boy from Bahawalpur. 3010 99

Hereditary adrenocorticotropin (ACTH) resistance syndromes encompass the genetically heterogeneous isolated or Familial Glucocorticoid Deficiency (FGD) and the distinct clinical entity known as Triple A syndrome. The molecular basis of adrenal resistance to ACTH includes defects in ligand binding, MC2R/MRAP receptor trafficking, cellular redox balance, cholesterol synthesis and sphingolipid metabolism. Biochemically, this manifests as ACTH excess in the setting of hypocortisolaemia. Triple A syndrome is an inherited condition involving a tetrad of adrenal insufficiency, achalasia, alacrima and neuropathy. FGD is an autosomal recessive condition characterized by the presence of isolated glucocorticoid deficiency, classically in the setting of preserved mineralocorticoid secretion. Primarily there are three established subtypes of the disease: FGD 1, FGD2 and FGD3 corresponding to mutations in the Melanocortin 2 receptor MC2R (25%), Melanocortin 2 receptor accessory protein MRAP (20%), and Steroidogenic acute regulatory protein STAR (5-10%) respectively. Together, mutations in these 3 genes account for approximately half of cases. Whole exome sequencing in patients negative for MC2R, MRAP and STAR mutations, identified mutations in minichromosome maintenance 4 MCM4, nicotinamide nucleotide transhydrogenase NNT, thioredoxin reductase 2 TXNRD2, cytochrome p450scc CYP11A1, and sphingosine 1-phosphate lyase SGPL1 accounting for a further 10% of FGD. These novel genes have linked replicative and oxidative stress and altered redox potential as a mechanism of adrenocortical damage. However, a genetic diagnosis is still unclear in about 40% of cases. We describe here an updated list of FGD genes and provide a description of relevant mouse models that, despite some being flawed, have been precious allies in the understanding of FGD pathobiology.
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PMID:Isolated glucocorticoid deficiency: Genetic causes and animal models. 3081 90

Triple A syndrome or Allgrove's syndrome is a rare autosomal recessive disorder usually manifested with three main clinical features, i.e. achalasia, alacrimation and adrenal inadequacy. Sometimes, it presents with polyneuropathy and neurological complications. Here, we report a case of a 7-year girl presenting with features of weight loss who was diagnosed with adrenal insufficiency at the age of 7 years while achalasia was diagnosed at the age of 3 years. First manifestation was achalasia and at that time, alacrimation was also defected. A 7-year XX female child presented at Endocrine Clinic of Armed Forces Institute of Pathology (AFIP) with hyperpigmentation, easy fatigue and weight loss. She had one sibling with same complaints and one brother died at the age of 3 years because of adrenal insufficiency. Her laboratory investigations revealed low cortisol level and high ACTH level, with inadequate response as well as short synacthen test (dynamic function test). This is a first case of Allgrove's syndrome reported in a tertiary hospital setting of Pakistan. Allgrove's syndrome should be considered in patients who report with adrenal insufficiency.
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PMID:A Child with Weight Loss and Alacrimation: Triple A Syndrome. 3114 22

Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. Various progressive neurological abnormalities and skin changes have been described in association with the syndrome. The disease is caused by mutation in the AAAS gene on chromosome 12q13. Mutations in AAAS were identified in more than 90% of individuals and families with TAS. The protein encoded by AAAS was termed ALADIN and is part of the WD repeat family of proteins, that have been found to be involved in many different functions such as protein-protein interaction, RNA processing, cytoskeleton assembly, control of cell division, signal transduction and apoptosis. Immunohistochemical analysis showed that mutated or truncated ALADIN localizes to the cytoplasm rather than to the nuclear pore complex. The exact function of ALADIN and the mechanisms that lead to the ACTH-resistant adrenal phenotype remains largely unknown. Nonetheless, recent studies provided some insights on the role of ALADIN as a member of the Nuclear Pore Complex not only implicated in the import of proteins involved in DNA repair and oxidative stress homeostasis but also in the strengthening of the mitotic spindle assembly. Early identification of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of the same family. In this review, we aim to summarize the current knowledge of clinical and molecular profile of patients with TAS and recommendations for the diagnosis, management, and follow-up of patients.
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PMID:Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity. 3253 14


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