Синдром Оллгрова в практике эндокринолога: сложности диагностики и особенности лечения
Синдром Оллгрова в практике эндокринолога: сложности диагностики и особенности лечения
Буйваленко У.В., Левшина А.Р., Еремкина А.К., Комшилова К.А., Платонова Н.М. Синдром Оллгрова в практике эндокринолога: сложности диагностики и особенности лечения. Терапевтический архив. 2024;96(10):978–982. DOI: 10.26442/00403660.2024.10.202869
Buyvalenko UV, Levshina AR, Eremkina AK, Komshilova KA, Platonova NM. Allgrove syndrome in endocrinology: Difficulties of diagnosis and treatment features. Case report. Terapevticheskii Arkhiv (Ter. Arkh.).
2024;96(10):978–982. DOI: 10.26442/00403660.2024.10.202869
Синдром Оллгрова в практике эндокринолога: сложности диагностики и особенности лечения
Буйваленко У.В., Левшина А.Р., Еремкина А.К., Комшилова К.А., Платонова Н.М. Синдром Оллгрова в практике эндокринолога: сложности диагностики и особенности лечения. Терапевтический архив. 2024;96(10):978–982. DOI: 10.26442/00403660.2024.10.202869
В клинической практике орфанные заболевания всегда связаны с определенными диагностическими трудностями. Синдром Оллгрова (Alacrimia, Achalasia, Adrenal insufficiency – AAAS) – редкое аутосомно-рецессивное мультисистемное заболевание, характеризующееся хронической надпочечниковой недостаточностью (НН), алакримией и ахалазией кардии, получившее название синдрома тройного А (триплета А). Наиболее тяжелыми его проявлениями являются ахалазия кардии и НН, которые часто определяют тяжесть течения заболевания. Большинство имеющихся научных данных по проблеме представлены описанием отдельных клинических случаев, а лечение подбирается индивидуально в соответствии с конкретными проявлениями заболевания. Прогноз в основном зависит от ранней диагностики синдрома. Учитывая редкость и высокую фенотипическую гетерогенность, необходимо повышать информированность врачей различных специальностей по данному синдрому, применять мультидисциплинарный подход. В статье представлен клинический случай пациента 22 лет с синдромом Оллгрова с выраженными проявлениями ахалазии кардии, НН, клинически значимыми неврологическими нарушениями.
Allgrove syndrome is a rare autosomal recessive disorder characterized by the achalasia, alacrimia, adrenal insufficiency, which gave the additional and more recognizable name of this pathology – “Triple-A syndrome”. The clinical presentation of classical signs and symptoms of the syndrome is dependent on the age of the patient. Ophthalmological abnormalities are usually present at birth, whereas adrenal and gastrointestinal abnormalities are apparent after six months to the first decade of life. Neurological dysfunction from the involvement of central or autonomic nervous systems is also common with Allgrove syndrome observed during the adolescent period. Genetic analysis and detection of the AAAS gene mutation is the main step in the diagnosis of the syndrome. The presented clinical case will demonstrate the difficulties in making a diagnosis, choosing a treatment strategy for a patient with a long history of Allgrove syndrome.
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3. Ates F, Vaezi MF. The Pathogenesis and Management of Achalasia: Current Status and Future Directions. Gut Liver. 2015;9(4):449-63. DOI:10.5009/gnl14446
4. Phillip M, Hershkovitz E, Schulman H. Adrenal insufficiency after achalasia in the triple-A syndrome. Clin Pediatr (Phila). 1996;35(2):99-100. DOI:10.1177/000992289603500208
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DOI:10.1530/EJE-08-0079
7. Kallabi F, Belghuith N, Aloulou H, et al. Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome. Arch Med Res. 2016;47(2):105-10. DOI:10.1016/j.arcmed.2016.04.004
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9. Dumic M, Barišic N, Kusec V, et al. Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. Eur J Pediatr. 2012;171(10):1453-9. DOI:10.1007/s00431-012-1745-1
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1. Allgrove J, Clayden GS, Grant DB, Macaulay JC. Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet. 1978;1(8077):1284-6. DOI:10.1016/s0140-6736(78)91268-0
2. Gazarian M, Cowell CT, Bonney M, Grigor WG. The “4A” syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. Eur J Pediatr. 1995;154(1):18-23. DOI:10.1007/BF01972967
3. Ates F, Vaezi MF. The Pathogenesis and Management of Achalasia: Current Status and Future Directions. Gut Liver. 2015;9(4):449-63. DOI:10.5009/gnl14446
4. Phillip M, Hershkovitz E, Schulman H. Adrenal insufficiency after achalasia in the triple-A syndrome. Clin Pediatr (Phila). 1996;35(2):99-100. DOI:10.1177/000992289603500208
5. Milenković T, Koehler K, Krumbholz M, et al. Three siblings with triple A syndrome with a novel frameshift mutation in the AAAS gene and a review of 17 independent patients with the frequent p.Ser263Pro mutation. Eur J Pediatr. 2008;167(9):1049-55. DOI:10.1007/s00431-007-0640-7
6. Collares CV, Antunes-Rodrigues J, Moreira AC, et al. Heterogeneity in the molecular basis of ACTH resistance syndrome. Eur J Endocrinol. 2008;159(1):61-8.
DOI:10.1530/EJE-08-0079
7. Kallabi F, Belghuith N, Aloulou H, et al. Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome. Arch Med Res. 2016;47(2):105-10. DOI:10.1016/j.arcmed.2016.04.004
8. Milenkovic T, Zdravkovic D, Savic N, et al. Triple A syndrome: 32 years experience of a single centre (1977–2008). Eur J Pediatr. 2010;169(11):1323-8. DOI:10.1007/s00431-010-1222-7
9. Dumic M, Barišic N, Kusec V, et al. Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. Eur J Pediatr. 2012;171(10):1453-9. DOI:10.1007/s00431-012-1745-1
10. Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet. 2001;10(3):283-90. DOI:10.1093/hmg/10.3.283
11. Tullio-Pelet A, Salomon R, Hadj-Rabia S, et al. Mutant WD-repeat protein in triple-A syndrome. Nat Genet. 2000;26(3):332-5. DOI:10.1038/81642
12. Cronshaw JM, Krutchinsky AN, Zhang W, et al. Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol. 2002;158(5):915-27. DOI:10.1083/jcb.200206106
13. Grigorieva G, Shestakov S. Transformation in the cyanobacterium Synechocystis sp. 6803. FEMS Microbiol Lett. 1982;13:367-70.
14. Hirano M, Furiya Y, Asai H, et al. ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome. Proc Natl Acad Sci U S A. 2006;103(7):2298-303. DOI:10.1073/pnas.0505598103
15. Storr HL, Kind B, Parfitt DA, et al. Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. Mol Endocrinol. 2009;23(12):2086-94. DOI:10.1210/me.2009-0056
16. Koehler K, Malik M, Mahmood S, et al. Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction. Am J Hum Genet. 2013;93(4):727-34. DOI:10.1016/j.ajhg.2013.08.002
17. Koehler K, Milev MP, Prematilake K, et al. A novel TRAPPC11 mutation in two Turkish families associated with cerebral atrophy, global retardation, scoliosis, achalasia and alacrima. J Med Genet. 2017;54(3):176-85. DOI:10.1136/jmedgenet-2016-104108
18. Vallet AE, Verschueren A, Petiot P, et al. Neurological features in adult Triple-A (Allgrove) syndrome. J Neurol. 2012;259(1):39-46. DOI:10.1007/s00415-011-6115-9
19. Sanyal D, Bhattacharjee S. A case of late-onset allgrove syndrome presenting with predominant autonomic dysfunction. Ann Indian Acad Neurol. 2013;16(2):266-8. DOI:10.4103/0972-2327.112494
20. Sarathi V, Shah NS. Triple-A syndrome. Adv Exp Med Biol. 2010;685:1-8. DOI:10.1007/978-1-4419-6448-9_1
21. Houlden H, Smith S, De Carvalho M, et al. Clinical and genetic characterization of families with triple A (Allgrove) syndrome. Brain. 2002;125(Pt. 12):2681-90. DOI:10.1093/brain/awf270
22. Fyodorov ED, Inoue H, Seleznev DE, et al. Peroral endoscopic myotomy in achalasia: methodology and immediate results of first intervention. Medical Council. 2015;(13):130-2 (in Russian). DOI:10.21518/2079-701X-2015-13-130-132
23. Barbieri LA, Hassan C, Rosati R, et al. Systematic review and meta-analysis: Efficacy and safety of POEM for achalasia. United European Gastroenterol J. 2015;3(4):325-34. DOI:10.1177/2050640615581732
24. Ivashkin VT, Truhmanov AS, Godzhello EhA, et al. Diagnostics and treatment of cardiac achalasia and cardiospasm: guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(4):36-54 (in Russian). DOI:10.22416/1382-4376-2016-4-36-54
25. Hallal C, Kieling CO, Nunes DL, et al. Diagnosis, misdiagnosis, and associated diseases of achalasia in children and adolescents: a twelve-year single center experience. Pediatr Surg Int. 2012;28(12):1211-7. DOI:10.1007/s00383-012-3214-3
26. Andrews CN, Anvari M, Dobranowski J. Laparoscopic Heller's myotomy or botulinum toxin injection for management of esophageal achalasia. Patient choice and treatment outcomes. Surg Endosc. 1999;13(8):742-6. DOI:10.1007/s004649901090
27. Maher JW. Thoracoscopic esophagomyotomy for achalasia. Surg Clin North Am. 2000;80(5):1501-10. DOI:10.1016/s0039-6109(05)70241-3
28. Iukina MIu, Troshina EA, Platonova NM, Bel'tsevich DG. Nadpochechnikovaia nedostatochnost'. In: Troshina EA. Sbornik metodicheskikh rekomendatsii (v pomoshch' prakticheskomu vrachu). Tver': Triada, 2017 (in Russian).
29. Litvitskiy PF. Pathocrinia. Etiology and pathogenesis: adrenal abnormalities. Current Pediatrics. 2011;10(5):63-73 (in Russian).
30. Yevsyutina YuV, Storonova OA, Trukhmanov AS, Ivashkin VT. Cardiac achalasia: modern concepts on etiology, pathogenesis, clinical presentation and diagnostics. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;(6):4-12 (in Russian).
31. Sheikh MM, Bittar K. Allgrove Syndrome. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2021.
1ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия; 2ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*ulibu@list.ru
________________________________________________
Uliana V. Buyvalenko*1, Anna R. Levshina2, Anna K. Eremkina1, Kseniya A. Komshilova1, Nadezhda M. Platonova1
1Endocrinology Research Centre, Moscow, Russia; 2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*ulibu@list.ru