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)

Achalasia of the cardia is an uncommon condition with an incidence of 0.1 cases per year per 100,000 population under 14 years. A review of experience at Booth Hall Children's Hospital over the past 10 years has revealed six cases of achalasia in children. This includes two cases of the rare syndrome of achalasia, alacrima and ACTH insensitivity (also known as Triple A syndrome) and its variants. There are 23 previously reported cases of Triple A syndrome and a further eight cases of its variants reported in the world literature. One-third of these cases (10 out of 31) have associated neurological abnormalities. The clinical and radiological features of achalasia are reviewed. The importance of barium studies in making the diagnosis is emphasized. However, early cases may show only spasm or incoordination, and manometry is required to confirm the diagnosis in these equivocal cases. In this series only three of the six barium studies were diagnostic and the remainder were diagnosed by manometry; all cases were subsequently confirmed by histology. Delay in diagnosis may result in severe lung damage due to repeated aspiration; this occurred in one of the six cases and was the cause of the child's death.
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PMID:Achalasia of the cardia in childhood and the syndrome of achalasia alacrima and ACTH insensitivity. 160 7

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

Achalasia of the esophagus is rare in children. The authors report eight cases and emphasize two atypical clinical records: The first one is a 3 month-old infant with respiratory distress and "near miss" Sudden Death Infant Syndrome. The second one is a ten year-old boy with association of achalasia of the esophagus, ACTH insensibility and alacryma. Theses cases are discussed.
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PMID:[Idiopathic achalasia of the esophagus in children. Report of 8 cases]. 221 98

A 10-year-old boy is described with a syndrome of adrenal insufficiency due to selective ACTH insensitivity associated with autonomic nervous system disorders. In addition to insufficient production of glucocorticoids and adrenal androgens, achalasia, defective lacrimation, anisocoria and hyperkeratosis of palms and soles we also found defective sweating, permanent cutis anserina and sensory polyneuropathy, which have not been reported previously in this rare syndrome.
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PMID:Selective ACTH insensitivity associated with autonomic nervous system disorders and sensory polyneuropathy. 282 65

A child is reported with adrenocortical unresponsiveness to ACTH and autonomic dysfunction. The latter consisted of cold extremities, progressive loss of tear production, the development of achalasia of the esophagus, pupillary dysfunction, and an abnormal histamine skin test. These findings suggest progressive parasympathetic denervation as a cause for the adrenocortical abnormality.
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PMID:Autonomic dysfunction and adrenocortical unresponsiveness to ACTH. 285 Mar 14

Four recent reports describe a multisystem disorder in which ACTH insensitivity is associated with achalasia and alacrima. We report studies on a male patient with this rare triad. The patient had alacrima from birth; isolated glucocorticoid deficiency had been diagnosed at 3.5 years of age and achalasia at age 6. The possibility that this syndrome could be due to a parasympathetic degeneration has already been proposed; the cause of the glucocorticoid deficiency, however, remains unclear. Parasympathetic function in other areas was investigated to determine whether there might be a more generalized abnormality. Specific cardiac tests of parasympathetic function showed that parasympathetic input to the heart was affected in the patient, while the same tests in an Addisonian child were normal. We show, then, a hitherto undetected parasympathetic abnormality in a patient with this syndrome, suggesting a generalized disturbance of this system. On this basis we may hypothesize that the glucocorticoid failure may be a consequence of the loss of parasympathetic input to the adrenal gland, although this remains to be demonstrated experimentally.
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PMID:Glucocorticoid deficiency with achalasia of the cardia and lack of lacrimation. 407 37

A number of patients with ACTH unresponsiveness resulting in glucocorticoid deficiency with normal mineralocorticoid activity have been described. This could be due to an inherited defect within the adrenal gland causing primary unresponsiveness to ACTH or to an inherited progressive degenerative process. The association of achalasia, lack of lacrimation, and glucocorticoid deficiency in two pairs of siblings with normal mineralocorticoid activity has been recently reported. Our case describes an 8.8-yr-old female with glucocorticoid insufficiency, partial mineralocorticoid deficiency, achalasia, and evidence of decreased lacrimation. Sodium depletion produced hyponatremia, and she was unable to increase her plasma aldosterone levels sufficiently, although PRA was markedly elevated. Our case may be part of a progressive degenerative process, possibly affecting both the autonomic nerve structures and the adrenal gland, leading not only to glucocorticoid deficiency but also to abnormal mineralocorticoid secretion.
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PMID:Glucocorticoid and partial mineralocorticoid deficiency associated with achalasia. 624 64

A 13-year-old boy, with the diagnosis of congenital adrenocortical unresponsiveness to ACTH (ACTH insensitivity) at age 7, developed a steppage gait, when under glucocorticoid replacement therapy at age 13. The parents were healthy and not consanguinous. On general physical examination, a mild diffuse skin hyperpigmentation was noted. Neurological examinations revealed that all the muscle stretch reflexes of both limbs were absent without pathologic reflexes. Pes cavus was found bilaterally. A slight decrease of tactile sensation was noted distal to the ankle joints. Pain sensation was slightly decreased in the toes. On laboratory examination, the conduction velocities of the left ulnar and median motor nerves were 51 and 45 m/sec, respectively, which are normal. No M-wave responses were obtained by electrical stimulation of the tibial and peroneal nerves. The coefficient of the variation of the R-R interval from ECG recordings was normal. Orthostatic hypotension was not observed. Achalasia was negative on the barium swallow esophagram. Therefore, it was concluded that he had motor and sensory polyneuropathy, and a right sural nerve biopsy was performed. A 12-year-old girl, a sister of the boy described above, with the diagnosis of ACTH insensitivity at age 5, noted a pain on the medial aspect of the left sole after skating. On general physical examination, a mild diffuse skin hyperpigmentation was discovered. On neurological examination, a spontaneous pain with dysesthesia was noted on the plantar aspect of the 1st, 2nd and 3rd left toes and on the anterior and medial aspect of the sole. Otherwise she was normal. A diagnosis of the left tarsal tunnel syndrome was made.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Two siblings with congenital adrenocortical unresponsiveness to ACTH showing peripheral neuropathy--morphometric evaluation of the sural nerve]. 792 65

Hereditary primary adrenal insufficiency syndromes due to ACTH resistance include hereditary glucocorticoid deficiency (HGD) and Allgrove's syndrome (AS). Patients with both conditions present in childhood with failure to thrive, weakness, and fatigue or adrenal crisis; patients with AS in addition have alacrima and achalasia (triple A syndrome). We studied four kindreds with HGD and four kindreds with AS for abnormalities of the ACTH receptor (ACTHR) gene. The ACTHR coding sequence in all AS kindreds and two HGD kindreds was normal. Analysis of the ACTHR gene of the proband in one of the HGD kindreds showed him to be homozygous for the previously described G221T transition causing a Ser74Ile substitution of the protein, which has been shown to inactivate the ACTHR in signal transduction. The proband in another HGD kindred was found to be a compound heterozygote with the G221T transition in one allele and a novel C818A transition in the other allele of ACTHR. The C818A transition caused the substitution of the highly conserved Pro273 by His in the receptor protein. In vitro expression of the mutated ACTHR in mouse melanoma M3 cells showed that at a medium ACTH concentration of 3 nM, cells transfected with the wild-type ACTHR produced twofold and threefold, respectively, of the amount of intracellular cAMP when compared to cells transfected with the ACTHR carrying the Pro273His and the Ser74Ile mutation, respectively, confirming that HGD in this kindred is caused by loss-of-function mutations of the ACTHR. These results showed that the genetic cause of the ACTH-resistant syndromes is heterogeneous.
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PMID:Genetic heterogeneity of adrenocorticotropin (ACTH) resistance syndromes: identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency. 975 16

Inherited adrenocorticotropin (ACTH) insensitivity syndromes comprise a group of rare diseases in which resistance to ACTH is either the sole feature or associated with other symptoms. This review focuses on two autosomal recessive disorders, familial glucocorticoid deficiency (FGD) (MIM*202200) and the triple A syndrome (MIM*231550), which have at least three different molecular aetiologies. In FGD, several missense mutations within the coding region of the ACTH receptor (MC2-R) have been identified in some, but not all patients, and segregation analyses and functional studies in a Y6 cell expression system confirmed that these mutations cause the disease. Some cases of FGD are not linked to the MC2-R locus on chromosome 18p11.2 suggesting genetic heterogeneity. The triple A syndrome is clinically characterized by the triad of adrenal insufficiency, achalasia and alacrima and a variety of neurological symptoms. After excluding several candidate genes we mapped this syndrome to a 6 cM interval on chromosome 12q13 with no indication for genetic heterogeneity. The identification of the gene(s) causing FGD without mutations in the MC2-R and causing the triple A syndrome may reveal novel aspects in cell signalling and neuroendocrinology.
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PMID:ACTH resistance syndromes. 1069 92


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