Achalasia Addisonianism Alacrimia syndrome

A hereditary disorder characterized by ACHALASIA, ADDISON DISEASE, and alacrima (a reduced or absent ability to secrete tears). Most affected individuals have all three of these features, although some have only two.Other disorders that may be present include DYSAUTONOMIA; INTELLECTUAL DISABILITY; SPEECH DISORDERS, a small head size, muscle weakness, movement problems, PERIPHERAL NEUROPATHY, and OPTIC ATROPHY. The neurological symptoms may worsen over time. Mutations in the AAAS gene have been identified. OMIM: 231550

Also Known As:

ACTH resistant adrenal insufficiency, achalasia and alacrima; Aaa Syndrome; Achalasia alacrimia syndrome; Achalasia-Addisonian Syndrome; Achalasia-Addisonianism-Alacrima Syndrome; Achalasia-Alacrima Syndrome; Acth-Resistant Adrenal Insufficiency, Achalasia And Alacrima; Addisonian achalasia syndrome; Addisonian-Achalasia Syndrome; Alacrima-Achalasia-Addisonianism; Alacrima-achalasia-adrenal insufficiency neurologic disorder; Allgrove syndrome; Glucocorticoid deficiency and achalasia; Hypoadrenalism with achalasia; Infantile achalasia with alacrima; Triple A syndrome; Triple-A Syndrome

Networked: 133 relevant articles (2 outcomes, 5 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Esophageal Achalasia (Megaesophagus)
2.	Achalasia Addisonianism Alacrimia syndrome
3.	Alacrima
4.	Adrenal Insufficiency (Adrenal Gland Hypofunction)
5.	Familial Glucocorticoid Deficiency 1

Experts

1.	Huebner, Angela: 15 articles (01/2018 - 02/2003)
2.	Koehler, Katrin: 12 articles (01/2018 - 03/2006)
3.	Huebner, A: 9 articles (02/2016 - 11/2000)
4.	Clark, Adrian J L: 6 articles (12/2009 - 12/2002)
5.	Koehler, K: 5 articles (02/2016 - 11/2004)
6.	Metherell, Louise A: 4 articles (01/2019 - 12/2006)
7.	Jühlen, Ramona: 4 articles (01/2018 - 01/2015)
8.	Handschug, K: 4 articles (05/2003 - 11/2000)
9.	Stratakis, Constantine A: 3 articles (01/2019 - 06/2004)
10.	Landgraf, Dana: 3 articles (01/2018 - 11/2016)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Achalasia Addisonianism Alacrimia syndrome:

1.	DNA (Deoxyribonucleic Acid)IBA 01/01/2013 - "DNA analysis is very helpful in establishing the final diagnosis of triple A syndrome, although its implication in the prediction of clinical expression and the outcome of the disorder is limited." 09/01/2008 - "We conclude that, although very helpful in establishing the final diagnosis of triple A syndrome, DNA analysis is not useful for the prediction of the clinical expression and outcome of the disorder. " 02/15/2003 - "We used classical and high-resolution chromosome analyses along with chromosome painting and DNA sequencing to study patients with triple A syndrome. " 01/01/2018 - "Later, they developed achalasia whereupon Allgrove syndrome was diagnosed clinically and confirmed by DNA sequencing which revealed a c.1331 + 1G > A mutation in the AAAS gene. " 03/01/2007 - "Five of the conditions (xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Down syndrome, and triple-A syndrome) display a defect in the nucleotide excision repair pathway, four (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) exhibit an unusual expansion of repeat sequences in DNA, and four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) exhibit defects in genes involved in repairing double-strand breaks. "
2.	Corticotropin Receptors (ACTH Receptor)IBA 07/01/1994 - "Gene linkage studies, however, show that the ACTH receptor is not associated with either a subgroup o f FGD in which mutations in the ACTH receptor gene cannot be found or with the triple-A syndrome. " 02/01/1991 - "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." 07/01/1998 - "In this short review, we describe the recent advances in the molecular biology of ACTH receptor genes, its post-receptor signal transduction in the adrenocortical cells, and the molecular genetics of the FGD and a related syndrome, Allgrove syndrome. " 07/01/1995 - "No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome." 03/01/1995 - "Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known. "
3.	Sulfhydryl Compounds (Thiols)IBA 01/01/2023 - "Patients with Triple-A syndrome had an increased level of thiol compared with healthy controls. " 01/01/2023 - "Triple-A syndrome patients had increased native thiol (SH), total thiol (SH+SS) concentrations, and native thiol/total thiol (SH/SH+SS) ratios than healthy controls. " 01/01/2023 - "This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with the Triple-A syndrome. " 01/01/2023 - "However, Triple-A syndrome patients had lowered disulfide (SS), disulfide/native thiol (SS/SH), and disulfide/total thiol (SS/SH+SS) ratios than the controls. " 01/01/2023 - "In addition, patients with the Triple-A syndrome were divided into 2 subgroups according to the mutation type, and their thiol and disulfide levels were compared. "
4.	Retinaldehyde (Retinal)IBA 01/01/2021 - "This is the first study to document retinal layer thicknesses in a series of patients with Triple A syndrome. "
5.	DisulfidesIBA 01/01/2023 - "This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with the Triple-A syndrome. " 01/01/2023 - "However, Triple-A syndrome patients had lowered disulfide (SS), disulfide/native thiol (SS/SH), and disulfide/total thiol (SS/SH+SS) ratios than the controls. " 01/01/2023 - "In addition, patients with the Triple-A syndrome were divided into 2 subgroups according to the mutation type, and their thiol and disulfide levels were compared. " 01/01/2023 - "We planned to investigate serum thiol/disulfide homeostasis, which is a part of redox hemostasis in patients with Triple-A syndrome. " 01/01/2023 - "The evaluation of thiol-disulfide homeostasis in children with Triple-A syndrome."
6.	Adrenocorticotropic Hormone (ACTH)FDA Link 11/01/2001 - "Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin." 12/01/1996 - "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. " 09/01/2011 - "The association of adrenocorticotropic hormone (ACTH) insensitivity with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare multisystem disorder. " 01/01/2005 - "The majority of authors attribute a limited contribution unless achalasia is related to a multisystem disorder, like the triple-A or Allgrove's syndrome, an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. " 01/01/1986 - "A 7-year-old male presented with a triple A syndrome, a tirad of ACTH insensitivity, achilasia and alacrima. "
7.	Proteins (Proteins, Gene)FDA Link 01/01/2023 - "Triple-A syndrome occurs due to the dysfunction of the ALADIN protein as a result of a mutation in the AAAS gene. " 01/01/2021 - "Protein ALADIN encoded by the AAAS gene is found to be defective in Triple A Syndrome. " 01/23/2018 - "Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. " 01/01/2018 - "Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. " 01/01/2015 - "Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. "
8.	GlucocorticoidsIBA 01/01/2019 - "Sequencing of the SGPL1 gene in 21 patients with familial glucocorticoid disease or triple A syndrome. " 11/01/2018 - "The syndrome includes two disorders inherited in an autosomal recessive fashion - familial glucocorticoid deficiency and triple A syndrome. " 01/01/2009 - "Adrenocorticotrophin resistance syndromes comprise familial glucocorticoid deficiency (FGD) and triple A syndrome, which are rare autosomal recessive diseases with distinct clinical features and molecular etiologies. " 01/01/2008 - "Unlike triple A syndrome which presents a range of clinical features, FGD is solely characterized by glucocorticoid deficiency. " 08/01/2007 - "The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. "
9.	Nuclear Pore Complex Proteins (Nucleoporins)IBA 12/01/2019 - "Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome." 03/01/2018 - "Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. " 01/01/2018 - "We could previously report that PGRMC2 interacts with the nucleoporin ALADIN which when mutated results in the autosomal recessive disorder triple A syndrome. " 02/01/2013 - "The triple A syndrome is a rare autosomal recessive disease caused by mutations in the AAAS gene, which encodes the nucleoporin ALADIN. " 11/06/2009 - "We show here that NDC1 directly interacts with the nucleoporin ALADIN, mutations of which are responsible for triple-A syndrome, and that this interaction is required for targeting of ALADIN to nuclear pore complexes (NPCs). "
10.	Hydrocortisone (Cortisol)FDA LinkGeneric 04/01/1999 - "Serum cortisol [correction of control] following replacement therapy in Triple A syndrome." 05/01/1995 - "[Achalasia, alacrimia and cortisol deficiency--Allgrove syndrome]." 02/01/2005 - "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. " 07/28/2022 - "ACTH and blood cortisol levels indicated an adrenal insufficiency, chest computed tomography and barium swallow test results indicated achalasia, tear break-up time as well as eye examination indicated alacrimia, which led to the diagnosis of triple A syndrome. "

Therapies and Procedures

1.	Therapeutics 04/01/2003 - "The authors present a family with three children affected with triple A syndrome--one had died, one was saved by diagnosis and timely therapy, and one was born after the diagnosis in the second child. " 04/01/1999 - "Serum control following replacement therapy in triple A syndrome - reply" 04/01/1999 - "Serum cortisol [correction of control] following replacement therapy in Triple A syndrome."
2.	Myotomy 07/06/2022 - "In the last 5 years, per-oral endoscopic myotomy (POEM) has proved highly successful in treating primary achalasia over the long term, but its long-term performance has not been certified by achalasia related to Triple A syndrome. " 07/06/2022 - "Triple A syndrome-related achalasia treated by per-oral endoscopic myotomy: Three case reports." 08/01/2018 - "With the diagnosis of Allgrove syndrome, a per-oral endoscopic myotomy (POEM) was performed for esophageal achalasia. " 08/01/2018 - "Per-oral endoscopic myotomy for esophageal achalasia in a case of Allgrove syndrome." 06/01/2020 - "Peroral endoscopic myotomy in a child with Triple A syndrome (Allgrove syndrome)."
3.	Fundoplication 08/01/1994 - "One patient suffering from an AAA syndrome (Achalasia/Alacrimia/ACTH deficiency) did not improve after Heller's procedure with Nissen fundoplication and dilatations. " 06/01/2014 - "We report a 7.7 kg infant with achalasia secondary to Allgrove syndrome who was successfully treated by Heller myotomy and simultaneous Toupet fundoplication. "
4.	Preoperative Period 01/01/2012 - "There wasnot property in the patient whom allgrove syndrome was excepted any steroid treatment in preoperative period. "
5.	Physical Therapy Modalities (Physical Therapy Technique) 09/01/2020 - "It appears that in this case, this patient with Allgrove syndrome demonstrated a significant increase in endurance, balance, and a return to functional activities and participation following a 10-week physical therapy program consisting of task-oriented exercise, aerobic training, postural control exercises, and patient education. "