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)

Isolated glucocorticoid failure associated with achalasia of the cardia is described in two pairs of siblings in separate families. Defective tear production is also present in three of the patients, and one shows other signs of autonomic dysfunction. Two other families with adrenal insufficiency and achalasia are known. This unusual association probably represents a familial disorder of as yet unknown aetiology.
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PMID:Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. 7 49

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

Adrenal insufficiency has been associated with adrenoleukodystrophy and adrenomyeloneuropathy. In these diseases, plasma very long chain fatty acids are elevated. Peripheral neuropathy is frequently seen in adults with adrenomyeloneuropathy. We encountered two first cousins with adrenal insufficiency, who also developed peripheral neuropathy, achalasia, alacrima, and microcephaly. However, plasma very long chain fatty acids, pipecolic acid, phytanic acid, and cranial computed tomographic scan were normal. Muscle mitochondrial respiratory chain enzymes were also normal. This syndrome of adrenal insufficiency, achalasia, alacrima, microcephaly, and peripheral neuropathy is different from either adrenomyeloneuropathy or adrenoleukodystrophy.
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PMID:Familial adrenal insufficiency, achalasia, alacrima, peripheral neuropathy, microcephaly, normal plasma very long chain fatty acids, and normal muscle mitochondrial respiratory chain enzymes. 800 62

Achalasia is a rare pathology in infancy. It is still more infrequent when associated with adrenal insufficiency and alacrima, a disorder known as Allgrove's syndrome, the etiology of which remains unclear. We describe a 9-year-old girl who presents with glucocorticoid insufficiency, partial mineralocorticoid deficiency, achalasia, and alacrima.
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PMID:Achalasia-alacrima-ACTH insensitivity syndrome (Triple-A-syndrome). 825 54

Achalasia is very uncommon in children. It is still more when it is associated with alacrima and adrenal insufficiency, a disorder known as Allgrove's Syndrome (Triple-A-Syndrome). This paper describes a 21-years-old man with lack of lacrimation, achalasia and glucocorticoid deficiency. Additional features included: Hyperreflexia, pes cavus, muscle weakness, and nasal speech. Indicating that the disorder has a wide spectrum of clinical manifestations. This case has been diagnosed at adulthood.
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PMID:[Allgrove syndrome (achalasia-alacrima-adrenal gland insufficiency): report of a case]. 892 56

The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.
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PMID:Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. 896 64

Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others.
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PMID:Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers. 928 47

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

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


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