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

This paper describes the progress of two previously reported brothers with familial glucocorticoid deficiency, achalasia of the cardia, and alacrima. In their early 'teens both boys developed polyneuropathy with sensory, motor and autonomic components, Parkinsonism, and signs of both dorsal column and pyramidal tract damage. The older boy also showed signs of dementia. Red cell folate levels were markedly reduced but plasma and CSF folate were normal. Serum B12 and erythrocyte concentrations were at or below the lower limit of normal CSF levels of homovanillic acid and 5-hydroxyindole acetic acid (the major metabolites of dopamine and serotonin in brain) were low, indicating impaired turnover of the two amines within the nervous system. Positron emission photometry scans in the older boy showed low binding of c-methyl-spiperone and reduced uptake of 18-F-L-fluorodopa in the striatum, confirming the impairment in dopamine metabolism and suggesting both reduced synthesis and reduced receptor density. Treatment with L-dopa up to 800 mg/day (along with carbidopa 200 mg/day) corrected the low CSF homovanillic acid levels and produced some improvement in the Parkinsonism but no other obvious clinical benefit. Empirical treatment with hydroxycobalamin (1000 micrograms three times a week) and folinic acid (15 mg/day) was without clinical effect. The cause of the neurological disorder, low red-cell folate concentrations, and amine disturbance remains unknown, as does the pathogenesis of the adrenocortical failure.
 ...
PMID:Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia. 153 68

Triple A syndrome is caused by mutations in the gene encoding ALADIN, leading to achalasia, alacrima and addisonism. Neurologic manifestations of the disease include motor neuron disease-like presentations, motor-sensory or autonomic neuropathy, optic atrophy, cerebellar ataxia, Parkinsonism, and mild dementia. We report a 60-year-old Japanese man with triple A syndrome. He was born to non-consanguineous parents. He underwent a surgical operation for achalasia at age 40, and thereafter, he developed a slowly progressive gait disturbance. Neurological examinations at age 60 revealed limb muscle wasting and weakness with pyramidal tract signs, distal-dominant sensory disturbance, optic atrophy, and autonomic dysfunction. Alacrima was detected using Schirmer test. All of these features were consistent with typical triple A syndrome. He lacked adrenal insufficiency that is frequently observed in patients with the classic phenotype of triple A syndrome. His sural nerve biopsy showed a moderate loss of myelinated fibers and hypomyelination. He was homozygous for a missense mutation, p.R155H, in the disease-causing gene, AAAS. Seven patients with genetically-confirmed, adult or late-onset triple A syndrome, including ours, have been reported to date. All the patients showed upper and lower motor neuron signs (100%), while sensory disturbance (29%) and autonomic dysfunction (57%) were less frequent. Careful assessment for alacrima followed by molecular genetic analysis of AAAS should be considered in patients who show a combined phenotype of motor neuron disease and sensory/autonomic disturbance, even in elderly patients.
 ...
PMID:Adult or late-onset triple A syndrome: case report and literature review. 2067 35

Allgrove syndrome (triple A) is a rare autosomal recessive disease. The classic triad includes, congenital adrenal insufficiency due to ACTH resistance, achalasia of the cardia and alacrimia. Neurological abnormalities are associated with autonomic neuropathy, sensory and motor defects, deafness, mental retardation, Parkinsonism and dementia. The gene responsible is the ADRACALIN or AAAS encoding a protein called ALADIN. We report a case of a 19 year-old male, assessed when he was 10 years old in our department due to suspected storage disease. Mild mental and language retardation, hypernasal voice, sensory-motor neuropathy with autonomic involvement and signs of spastic paraparesis, alacrimia. gastroesophageal reflux, and achalasia. Molecular studies showed to mutations, the undescribed p.Tyr 19 Cys, and IVS14 +1 G.
 ...
PMID:[Allgrove syndrome (triple A). Finding of a mutation not described in the AAAS gene]. 2282 7

Swallowing occurs in 3 phases: oral, pharyngeal, and esophageal. Oropharyngeal dysphagia typically is a result of neuromuscular disorders, such as stroke and parkinsonism, or of mucosal dryness caused by drugs or radiation therapy. Esophageal dysphagia is commonly caused by anatomic defects of the esophagus, such as reflux disease; motility disorders, such as achalasia; or eosinophilic esophagitis. If oropharyngeal dysphagia is suspected, the patient should undergo initial testing with a water or semisolid bolus swallow test. If results are positive, the diagnosis can be confirmed with a videofluoroscopic swallowing study. If esophageal dysphagia is suspected, patients typically undergo endoscopic esophagogastroduodenoscopy. Management of confirmed oropharyngeal dysphagia involves short-term compensation strategies, such as postural changes or food thickening, to minimize the risk of aspiration. This is followed by rehabilitation that may involve swallowing exercises with biofeedback or electrical stimulation of the swallowing muscles. Some patients may need enteral feeding. For esophageal dysphagia, choice of management depends on the etiology; it may include endoscopic dilation, myotomy, injection of onabotulinumtoxinA (formerly called botulinum toxin type A) for structural abnormalities, or topical steroid therapy for eosinophilic esophagitis.
...
PMID:Common gastrointestinal symptoms: dysphagia. 2412 2