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)

Allgrove syndrome (isolated glucocorticoid deficiency, achalasia and alacrima) was found in eight members of an inbred French Canadian/North American Indian pedigree. The high degree of consanguinity supports an autosomal recessive mode of inheritance for this disorder. Six patients presented with hypoglycaemia and other evidence of cortisol deficiency between 2.5 and 8 years of age; however, two others became cortisol deficient after initial testing showed normal cortisol responses to ACTH, evidence that the glucocorticoid insufficiency of this syndrome may not be congenital, but may develop as late as the third decade. No evidence of mineralocorticoid deficiency has been found during 65 patient-years of follow-up. Alacrima was the earliest and most consistent clinical sign of Allgrove syndrome. Other manifestations of peripheral or autonomic neuropathy were found in four patients. The patients showed similar facial features, and three had significant velo-pharyngeal incompetence. All showed oesophageal dysmotility even in the absence of symptomatic dysphagia. In-vitro studies of lymphocyte ACTH binding showed no differences from normal controls. If such lymphocyte binding, as has been suggested, reflects adrenal ACTH receptor activity, these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor. However, the observation that ACTH does not elicit increased adenylate cyclase activity even in normal lymphocytes casts considerable doubt on the physiological significance of ACTH binding to lymphocytes. It seems likely, therefore, that true ACTH receptors are not expressed on peripheral lymphocytes, and any conclusions regarding a possible receptor defect in Allgrove syndrome must await studies of receptor expression on adrenal cell membranes.
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PMID:Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima. 185 Jun 71

Autonomic nervous function in achalasia of the cardia was assessed by measuring the response of the lower oesophageal sphincter to abdominal compression, the gastric secretory response to insulin-induced hypoglycaemia and the pulse rate variability with deep respiration. Twenty-eight patients with symptomatic achalasia and 24 age and sex-matched control subjects were studied. Rise in intra-abdominal pressure normally causes a rise in lower oesophageal pressure through a vagally-mediated mechanism. Before treatment this response was unimpaired in eight of 10 patients with achalasia. A sub-normal response was found in eight of 10 patients who had previously had pneumatic dilatation of the cardia and in three of four who had had a cardiomyotomy. These abnormalities reflected the effect of treatment in disrupting the sphincter rather than impairment of its innervation. The gastric acid secretory response to insulin-induced hypoglycaemia, expressed as a ratio of that to pentagastrin, was normal in each of the nine patients studied. Pulse rate variability with deep respiration, a test of cardiac vagal function, was normal in 22 of 25 patients studied. It is concluded that in achalasia the vagal trunks appear functionally intact and that the myenteric plexus lesion rarely affects the responsiveness of the lower oesophageal sphincter to increase in intra-abdominal pressure.
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PMID:Vagal function in achalasia of the cardia. 368 43

Familial isolated glucocorticoid deficiency is a form of potentially lethal hereditary unresponsiveness to ACTH that manifests as primary adrenal insufficiency, usually without mineralocorticoid deficiency. Affected children commonly present with hyperpigmentation, recurrent hypoglycemia, chronic asthenia and failure to thrive within the first 2 years of life. Typically, they have deficient production of cortisol and adrenal androgens in the presence of markedly elevated ACTH levels, while renin and aldosterone levels are usually normal and responsive to activation of the renin-angiotensin axis. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many, but not all, affected families. Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor. Discovery of the molecular defect(s) responsible for isolated glucocorticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome (adrenal insufficiency, alacrima, achalasia) will hopefully provide further insight into the mechanisms of adrenocortical function and will increase the prospect of new therapeutic approaches.
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PMID:Isolated glucocorticoid deficiency and ACTH receptor mutations. 1071 60

Allgrove syndrome is a genetic disorder inherited in an autosomal recessive pattern and characterized by a triad of adrenal insufficiency, achalasia, and alacrima. The gene affected by the mutation in patients with Allgrove syndrome is termed either AAAS or ALADIN (alacrima/achalasia/adrenal insufficiency/neurologic disorder). Adrenal insufficiency in patients with this disorder may develop as late as the third decade of life. We describe a 24-year-old female with Allgrove syndrome, in whom initial testing with 250 microg corticotropin (ACTH) stimulation test performed on 3 occasions produced normal serum cortisol values and results of the 1-microg ACTH stimulation tests performed on 6 occasions were conflicting. Insulin-induced hypoglycemia produced a nadir serum glucose value of 36 mg/dL without adequate serum cortisol stimulation, confirming presence of adrenal insufficiency. Gene sequencing identified 2 mutations in the triple A gene: an IVSC14 + 1 G to A mutation, which has been previously reported, and a novel R155P exon 6 mutation. We conclude that a novel R155P mutation in the ALADIN gene is associated with Allgrove syndrome and that insulin-induced hypoglycemia, rather than ACTH stimulation tests, should be used for accurate diagnosis of adrenal insufficiency in this disorder.
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PMID:The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene. 1569 Mar 14

We report on the first Chinese patient with triple-A syndrome, who presented at 22 months with status epilepticus secondary to hyponatraemia and hypoglycaemia. Subsequent endocrine investigations confirmed primary adrenal insufficiency and aldosterone deficiency. In the presence of achalasia and alacrima, this patient satisfies the diagnostic criteria of triple-A syndrome. Further molecular testing detected compound heterozygous mutations in the AAAS gene: a c.580C --> T transition in exon 7 and a c.771delG single nucleotide deletion in exon 8. Testing of parents and brother confirmed their heterozygous carrier status.
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PMID:Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS gene. 1678 45

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder, in 40% of patients caused by mutation in the ACTH receptor gene. In the remaining affected persons most probably mutation refers to regulatory region of ACTH receptor or other factors responsible for differentiation of the adrenal cortex. FGD is characterized by elevated ACTH and low serum morning cortisol level that does not respond to exogenous ACTH stimulation. Mineralocorticoid function remains unaffected. Clinical symptoms of FGD are due to glucocorticoid deficiency and are manifested in infancy or early childhood. Typically they include skin hyperpigmentation, failure to thrive, hypoglycaemia, which in some children may be lethal. Allgrove's syndrome, is considered to be a separate condition, characterized by glucocorticoid deficiency along with alacrimia, achalasia and neurological deficits. Treatment of FGD includes substitution of glucocorticoids with dose adjustment depending on the clinical state. Such treatment usually prevents from hypoglycaemia and provides normal growth and development of the patient.
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PMID:[Familial glucocorticoid deficiency]. 1788 Aug 14

Achalasia cardia is an infrequent disorder of esophageal dysmotility that has failure of the lower end of the esophagus to relax with swallowing as hallmark abnormality. Diabetes mellitus, on the other hand, can afflict the motor activity of gastrointestinal tract by causing autonomic neuropathy. Combination of these diseases can be very distressing to a patient. We present a 45-year-old lady co-affected with both these disorders who presented with severe hypoglycemia and was managed successfully using the multiple strategies to treat achalasia and diabetes.
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PMID:Brittleness of diabetes due to achalasia cardia managed successfully by multiple innovative strategies. 2425 Dec 7