Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Allgrove syndrome or triple A (3A) syndrome is a multisystem disorder which classically involves the triad of esophageal achalasia, alacrima, and adrenal insufficiency due to adrenocorticotropin hormone insensitivity. It follows an autosomal recessive pattern of inheritance and is associated with mutations in the AAAS (achalasia-addisonianism-alacrima syndrome) gene. Since its first description in 1978, the knowledge on clinical and genetic characteristics has been expanding; however, the current literature is limited to case reports and case reviews. Early recognition of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of kin. The coordination of care for these patients requires a multidisciplinary team of specialists, including endocrinologists, neurologists, gastroenterologists, ophthalmologists, developmental specialists, dentists, geneticists, and surgeons. In this review, we aim to summarize the current recommendations for the diagnosis, management, and follow-up of patients with 3A syndrome.
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PMID:Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach. 3169 56


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