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)

Familial glucocorticoid deficiency is a rare multisystem disorder characterized by glucocorticoid deficiency with normal mineralocorticoid activity, achalasia of the cardia, and alacrima. Familial hypophosphatemic rickets is characterized by selective renal phosphate wasting with subsequent hypophosphatemia and an inappropriately low 1,25-dihydroxyvitamin D concentration for the degree of hypophosphatemia. A 6-year-old girl with both disorders is described. A biochemical relationship between familial glucocorticoid deficiency and familial hypophosphatemic rickets could not be defined; the influence of cortisol on her serum calcium level, phosphorus level, and rickets, as well as the natural history of these two entities, is described.
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PMID:Familial glucocorticoid deficiency in a girl with familial hypophosphatemic rickets. 339 83

Cricopharyngeal dysfunction is a relatively uncommon disorder that is widely misunderstood. Cricopharyngeal dysmotility is thought to represent abnormal function of the upper esophageal or cricopharyngeal sphincter. The cause of this dysfunction is related to uncoordinated pharyngeal swallowing, achalasia, or a combination of these factors. Unfortunately, standard diagnostic tests have not consistently demonstrated a failure of the cricopharyngeal sphincter to malfunction; therefore, cricopharyngeal myotomy has been suggested as a diagnostic and therapeutic tool in the treatment of dysmotility. Our report focuses on the current trends in the diagnosis and treatment of cricopharyngeal dysfunction. We also present a case report of a transmucosal cricopharyngeal myotomy performed with the potassium-titanyl-phosphate (KTP) laser. The KTP laser was found to be relatively safe and effective and did not demonstrate significant morbidity. Our conclusion was that a transmucosal cricopharyngeal myotomy with the KTP laser may represent a viable alternative for patients with cricopharyngeal dysmotility.
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PMID:Transmucosal cricopharyngeal myotomy with the potassium-titanyl-phosphate laser in the treatment of cricopharyngeal dysmotility. 812 32

Cricopharyngeal dysfunction is a relatively uncommon disorder that is misunderstood by many physicians. Cricopharyngeal dysmotility is thought to indicate abnormal function in the upper esophageal or cricopharyngeal sphincter, the etiology of which is related to uncoordinated pharyngeal swallowing, achalasia, or a combination of these factors. Unfortunately, standard diagnostic tests do not consistently show that the cricopharyngeal sphincter malfunctions; so cricopharyngeal myotomy has been suggested as a diagnostic and therapeutic tool in the treatment of dysmotility. The current report reviews trends in the diagnosis and treatment of cricopharyngeal myotomy, including the results of cricopharyngeal myotomy using the potassium-titanyl-phosphate (KTP) laser. A transmucosal cricopharyngeal myotomy with the KTP laser may be a viable alternative for patients with cricopharyngeal dysmotility compared with conventional techniques.
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PMID:The treatment of cricopharyngeal dysmotility with a transmucosal cricopharyngeal myotomy using the potassium-titanyl-phosphate (KTP) laser. 954 45

GMPPA encodes the GDP-mannose pyrophosphorylase A protein (GMPPA). The function of GMPPA is not well defined, however it is a homolog of GMPPB which catalyzes the reaction that converts mannose-1-phosphate and guanosine-5'-triphosphate to GDP-mannose. Previously, biallelic mutations in GMPPA were reported to cause a disorder characterized by achalasia, alacrima, neurological deficits, and intellectual disability. In this study, we report a female proband with achalasia, alacrima, hypohydrosis, apparent intellectual disability, seizures, microcephaly, esotropia, and craniofacial dysmorphism. Exome sequencing identified a previously unreported homozygous c.853+1G>A variant in GMPPA in the proband and her affected sister. Their unaffected parents were heterozygous, and unaffected brother homozygous wild type for this variant. Lymphoblast cells from the affected sisters showed complete loss of the GMPPA protein by Western blotting, and increased levels of GDP-mannose in lymphoblasts on high performance liquid chromatography. Based on our findings and the previous report describing patients with an overlapping phenotype, we conclude that this novel variant in GMPPA, identified by exome sequencing in the proband and her affected sister, is the genetic cause of their phenotype and may expand the known phenotype of this recently described glycosylation disorder.
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PMID:A novel mutation in GMPPA in siblings with apparent intellectual disability, epilepsy, dysmorphism, and autonomic dysfunction. 2857 18

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