Користувач:Aspilemetala/Чернетка/Альфа-таласемія

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Альфа-таласемія
Шаблон успадкування альфа-таласемії
Шаблон успадкування альфа-таласемії
Шаблон успадкування альфа-таласемії
Інші назви α-таласемія
Симптоми Жовтяниця, втома[1]
Причини Делеції у хромосомі 16[2]
Метод діагностики Електрофорез гемоглобіна[3]
Лікування Переливання крові, можлива спленектомія[1][4]
Класифікація та зовнішні ресурси

Альфа-таласемія (α-таласемія) - форма таласемії, яка залучає гени HBA1[5] і HBA2[6]. Таласемії є групою спадкових станів крові, що призводить до пошкодження вироблення гемоглобіну, молекули, що переносить кисень у крові[7]. Нормальний гемоглобін складається з двох α-ланцюгів і двох β-ланцюгів; при альфа-таласемії кількість α-ланцюгів зменшується, призводячи до зменшення нормального гемоглобіну. Окрім того, альфа-таласемія призводить до вироблення нестабільних молекул β-глобіну (із яких кладається β-ланцюг), що веде до підвищеного руйнування еритроцитів. Ступінь пошкодження ґрунтується на клінічному фенотипі (скільки генів пошкоджено)[3].

Ознаки та симптоми[ред. | ред. код]

Ознаки та симптоми альфа-таласемії[8][9][10]
Поширені Непоширені
  • Анемія: У людей із альфа-таласемією можуть спостерігатися як зниження вироблення еритроцитів, так і збільшення їх руйнування, що може призводити до таких симптомів як утома та запаморочення[11]
  • Спленомегалія
  • Жовчні камені
  • Відкладене зростання

Cause[ред. | ред. код]

Alpha-thalassemias are most commonly inherited in a Mendelian recessive manner. They are also associated with deletions of chromosome 16p.[2] Alpha thalassemia can also be acquired under rare circumstances.[12]

Pathophysiology[ред. | ред. код]

The mechanism sees that α thalassemias results in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers called hemoglobin H or HbH of four beta chains. The excess γ chains form tetramers which are poor carriers of O2 since their affinity for O2 is too high, so it is not dissociated in the periphery. Homozygote α0 thalassaemias, where numerous γ4 but no α-globins occur at all (referred to as Hb Barts), often result in death soon after birth.[3][1][13]

Diagnosis[ред. | ред. код]

Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and molecular diagnosis. Alpha-thalassemia can be mistaken for iron-deficiency anaemia on a full blood count or blood film, as both conditions have a microcytic anaemia. Serum iron and serum ferritin can be used to exclude iron-deficiency anaemia.[3]

Types[ред. | ред. код]

Two genetic loci exist for α globin, thus four alleles are in diploid cells. Two alleles are maternal and two alleles are paternal in origin. The severity of the α-thalassemias is correlated with the number of affected α-globin alleles: the greater, the more severe will be the manifestations of the disease. When noting the genotype, an "α" indicates a functional alpha chain, and '-' a pathological one.[1][13]

Alleles affected Description Genotype
One This is known as alpha thalassemia silent and with this type, the effect on hemoglobin synthesis is minimal. Three α-globin genes are enough to permit normal hemoglobin production, and no clinical symptoms present. It occurs due to a deletion or non-deletion mutation.[1] - α/α α
Two
Haematopoiesis(production of blood cells)

The condition is called alpha thalassemia trait; two α genes permit nearly normal production of red blood cells, but a mild microcytic hypochromic anemia is seen. The disease in this form can be mistaken for iron-deficiency anemia and treated inappropriately with iron.[3][1]

Alpha-thalassemia trait can exist in two forms:[1]

  • Alpha-thal-1 (- -/α α), involves cis deletion of both alpha genes on the same chromosome. Higher incidence in people of Asian descent when compared with the general population.
  • Alpha-thal-2 (- α/- α), involves trans deletion of alpha genes; this occurs on different (homologous) chromosomes. Higher incidence in people of African descent when compared with the general population.
 - -/α α
or
- α/- α
Three This condition is called hemoglobin H disease; two unstable hemoglobins are present in the blood; hemoglobin Barts (tetrameric γ chains) and hemoglobin H (tetrameric β chains). Both of these unstable hemoglobins have a higher affinity for oxygen than normal hemoglobin.[14] A microcytic hypochromic anemia with target cells and Heinz bodies (precipitated HbH) on the peripheral blood smear can occur, as well as hepatosplenomegaly. The disease is noticed in childhood or in early adult life; anemia and hepatosplenomegaly are noted.Шаблон:Medical citation needed - -/- α
Four This is known as alpha thalassemia major; these fetuses are edematous, have little circulating hemoglobin, and the hemoglobin that is present is all tetrameric γ chains. When all four alleles are affected, the fetus likely will not survive gestation without in utero intervention; most infants with alpha-thalassemia major are stillborn with hydrops fetalis. Fetuses treated with intrauterine transfusions throughout pregnancy starting at an early gestational age can survive to birth with acceptable morbidity. After birth, the treatment options include bone marrow transplantation or continued chronic transfusions.[15] - -/- -
α α/α α = normal: 'α α' before the '/' represents one chromosome, and 'α α' after the '/', its homologous chromosome.

Laboratory diagnosis[ред. | ред. код]

The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions).[джерело?]

Deletion of four alpha globin genes was previously felt to be incompatible with life, but there are currently 69 patients who have survived past infancy. All such children too show high level of hemoglobin Barts on newborn screen along with other variants.[16]

Post-newborn ages, initial laboratory diagnosis should include a complete blood count and red blood cell indices.[8] As well, a peripheral blood smear should be carefully reviewed.[8] In hemoglobin H disease, red blood cells containing hemoglobin H inclusions can be visualized on the blood smear using new methylene blue or brilliant cresyl blue stain.[17]

Hemoglobin analysis is important for the diagnosis of alpha-thalassemia as it determines the types and percentages of types of hemoglobin present.[18] Several different methods of hemoglobin analysis exist, including hemoglobin electrophoresis, capillary electrophoresis and high-performance liquid chromatography.[18]

Molecular analysis of DNA sequences (DNA analysis) can be used for the confirmation of a diagnosis of alpha-thalassemia, particularly for the detection of alpha-thalassemia carriers (deletions or mutations in only one or two alpha-globin genes).[18]

Treatment[ред. | ред. код]

Treatment for alpha-thalassemia may include blood transfusions to maintain hemoglobin at a level that reduces symptoms of anemia. The decision to initiate transfusions depends on the clinical severity of the disease.[19] Splenectomy is a possible treatment option to increase total hemoglobin levels in cases of worsening anemia due to an overactive or enlarged spleen, or when transfusion therapy is not possible.[20] However, splenectomy is avoided when other options are available due to an increased risk of serious infections and thrombosis.[20]

Additionally, gallstones may be a problem that would require surgery. Secondary complications from febrile episode should be monitored, and most individuals live without any need for treatment.[1][4] Additionally, stem cell transplantation should be considered as a treatment (and cure), which is best done in early age. Other options, such as gene therapy, are still being developed.[21]

A study by Kreger et al combining a retrospective review of three cases of alpha thalassemia major and a literature review of 17 cases found that in utero transfusion can lead to favorable outcomes. Successful hematopoietic cell transplantation was eventually carried out in four patients.[22]

Epidemiology[ред. | ред. код]

Malaria

Worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role. Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean Basin, and generally tropical (and subtropical) regions. The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. More specifically, HbH disease is seen in Southeast Asia and the Middle East, while Hb Bart hydrops fetalis is acknowledged in Southeast Asia only.[23] The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes.[24]

Див. також[ред. | ред. код]

Примітки[ред. | ред. код]

  1. ↑ а б в г д е ж и Origa, Raffaella; Moi, Paolo; Galanello, Renzo; Cao, Antonio (1 January 1993). Alpha-Thalassemia. GeneReviews. PMID 20301608. Процитовано 22 September 2016.update 2013
  2. ↑ а б BRS Pathology (вид. 4th). Lippincott Williams & Wilkins medical. December 2009. с. 162. ISBN 978-1451115871.
  3. ↑ а б в г д Alpha Thalassemia Workup: Approach Considerations, Laboratory Studies, Hemoglobin Electrophoresis. emedicine.medscape.com. Процитовано 24 травня 2016.
  4. ↑ а б Complications and Treatment | Thalassemia | Blood Disorders | NCBDDD | CDC. www.cdc.gov. Процитовано 22 September 2016.
  5. ↑ OMIM 141800
  6. ↑ OMIM 141850
  7. ↑ Lanzkowsky's Manual Of Pediatric Hematology And Oncology 6th Edition ( 2016) (англ.).
  8. ↑ а б в г д Alpha-thalassemia - Symptoms, diagnosis and treatment | BMJ Best Practice. bestpractice.bmj.com. Процитовано 17 листопада 2019.
  9. ↑ Reference, Genetics Home. Alpha thalassemia. Genetics Home Reference (англ.). Процитовано 25 листопада 2019.
  10. ↑ Origa, Raffaella; Moi, Paolo (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (ред.), Alpha-Thalassemia, GeneReviews®, University of Washington, Seattle, PMID 20301608, процитовано 25 листопада 2019
  11. ↑ Assessment of anaemia - Aetiology | BMJ Best Practice. bestpractice.bmj.com. Процитовано 25 листопада 2019.
  12. ↑ Steensma DP, Gibbons RJ, Higgs DR (January 2005). Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood. 105 (2): 443—52. doi:10.1182/blood-2004-07-2792. PMID 15358626.
  13. ↑ а б Galanello R, Cao A (February 2011). Gene test review. Alpha-thalassemia. Genetics in Medicine. 13 (2): 83—8. doi:10.1097/GIM.0b013e3181fcb468. PMID 21381239.
  14. ↑ Hemoglobin H disease. Orphanet. Процитовано 22 September 2016.
  15. ↑ Vichinsky EP (1 січня 2009). Alpha thalassemia major--new mutations, intrauterine management, and outcomes. Hematology. American Society of Hematology. Education Program. 2009 (1): 35—41. doi:10.1182/asheducation-2009.1.35. PMID 20008180.
  16. ↑ Songdej D, Babbs C, Higgs DR (March 2017). An international registry of survivors with Hb Bart's hydrops fetalis syndrome. Blood. 129 (10): 1251—1259. doi:10.1182/blood-2016-08-697110. PMC 5345731. PMID 28057638.
  17. ↑ Keohane, E; Smith, L; Walenga, J (2015). Rodak's Hematology: Clinical Principles and Applications (вид. 5). Elsevier Health Sciences. с. 466. ISBN 978-0-323-23906-6.
  18. ↑ а б в Viprakasit, Vip; Ekwattanakit, Supachai (1 квітня 2018). Clinical Classification, Screening and Diagnosis for Thalassemia. Hematology/Oncology Clinics of North America. Thalassemia. 32 (2): 193—211. doi:10.1016/j.hoc.2017.11.006. ISSN 0889-8588. PMID 29458726.
  19. ↑ UpToDate. www.uptodate.com. Процитовано 25 листопада 2019.
  20. ↑ а б Taher, Ali; Musallam, Khaled; Cappellini, Maria Domenica, ред. (2017). Guidelines for the management of non-transfusion-dependent thalassemia (NTDT) (вид. 2nd). Thalassemia International Foundation. с. 24—32. Процитовано 5 листопада 2019.
  21. ↑ Thalassaemia | Doctor | Patient. Patient. Процитовано 22 September 2016.
  22. ↑ Kreger EM, Singer ST, Witt RG, Sweeters N, Lianoglou B, Lal A, Mackenzie TC, Vichinsky E (December 2016). Favorable outcomes after in utero transfusion in fetuses with alpha thalassemia major: a case series and review of the literature. Prenatal Diagnosis. 36 (13): 1242—1249. doi:10.1002/pd.4966. PMID 27862048. S2CID 29734120. {{cite journal}}: Недійсний |display-authors=6 (довідка)
  23. ↑ Harteveld CL, Higgs DR (May 2010). Alpha-thalassaemia. Orphanet Journal of Rare Diseases. 5 (1): 13. doi:10.1186/1750-1172-5-13. PMC 2887799. PMID 20507641.{{cite journal}}: Обслуговування CS1: Сторінки із непозначеним DOI з безкоштовним доступом (посилання)
  24. ↑ Haematology Made Easy. AuthorHouse. 2013-02-06. ISBN 9781477246511.page 246

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