Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 126-131
Геморрагическая тромбоцитопатия с дефектом сигнализации CalDAG-GEFI
https://doi.org/10.24287/1726-1708-2021-20-3-126-131Аннотация
Геморрагическая тромбоцитопатия с дефектом сигнализации тромбоцитов CalDAG-GEFI является редким заболеванием, связанным с мутацией в гене RASGRP2. К настоящему времени имеются сведения о данном заболевании у не менее чем 10 человек в мире. Мы представляем описание клинического наблюдения данной патологии у ребенка 9 лет, а также предлагаем анализ доступной литературы, посвященной патогенетическим аспектам, клиническим проявлениям и распространенности этого редкого заболевания. Родители пациентки дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.
Список литературы
1. McGarry G.W. Recurrent epistaxis in children. BMJ Clin Evid 2013; 2013: 0311.
2. Carpenter R.F. The prevalence and distribution of bruising in babies. Arch Dis Child 1999; 80: 363–6.
3. Collins P.W., Hamilton M., Dunstan F.D., Maguire S., Nuttall D.E., Liesner R., et al. Patterns of bruising in preschool children with inherited bleeding disorders: a longitudinal study. Arch Dis Child 2017; 102: 1110–7.
4. Downes A.J., Crossland D.S., Mellon A.F. Prevalence and distribution of petechiae in well babies. Arch Dis Child 2002; 86: 291–2.
5. Soheilifar J., Ahmadi M., Ahmadi M., Mobaien A.R. Prevalence and location of petechial spots in well infants. Arch Dis Child 2010; 95: 518–20.
6. Lambert M.P. Inherited Platelet Disorders: A Modern Approach to Evaluation and Treatment. Hematol Oncol Clin North Am 2019; 33 (3): 471–87. doi: 10.1016/j.hoc.2019.01.008
7. Федорова Д.В., Жарков П.А., Игнатова A.А., Федотов А.Ю., Полохов Д.М., Полетаев А.В. и др. Диагностика тромбоцитопатий у детей: корреляции исследования функциональной активности тромбоцитов с клинической картиной и результатами агрегометрии. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2018; 17 (1): 16–22.
8. Свирин П.В., Тернавский А.П., Вдовин В.В., Ларина Л.Е., Ражева А.С., Лившиц А.М. и др. Распространенность геморрагических проявлений у московских детей школьного возраста. Педиатрия. Журнал им. Г.Н. Сперанского 2011; 90 (4): 43–7.
9. Siddiq S., Clark A., Mumford A. Haemophilia. A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia. Available at: http://thrombo.cambridgednadiagnosis.org.uk/gene-disorder-list/. Accessed October 1, 2018.
10. Bowman M., Riddel J., Rand M.L., Tosetto A., Silva M., James P.D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire. J Thromb Haemost 2009; 7 (8): 1418–21.
11. Cifuni S.M., Wagner D.D., Bergmeier W. CalDAGGEFI and protein kinase C represent alternative pathways leading to activation of integrin aIIbb3 in platelets. Blood 2008; 112 (5): 1696–703.
12. Kawasaki H., Springett G.M., Toki S., Canales J.J., Harlan P., Blumenstiel J.P., et al. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A 1998; 95: 13278–83.
13. Crittenden J.R., Bergmeier W., Zhang Y., Piffath C.L., Liang Y., Wagner D.D., et al. CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 2004; 10 (9): 982–6.
14. Canault M., Ghalloussi D., Grosdidier C., Guinier M., Perret C., Chelghoum N., et al. Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding. J Exp Med 2014; 211 (7): 1349–62.
15. Lagarrigue F., Kim C., Ginsberg M.H. The Rap1-RIAMtalin axis of integrin activation and blood cell function. Blood 2016; 128 (4): 479–87.
16. Stefanini L., Paul D.S., Robledo R.F., Chan E.R., Getz T.M., Campbell R.A., et al. RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J Clin Invest 2015; 125 (4): 1419–32.
17. Cattaneo M. The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 2011; 117 (7): 2102– 12.
18. Lozano M.L., Cook A., Bastida J.M., Paul D.S., Iruin G., Cid A.R., et al. Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction. Blood 2016; 128 (9): 1282–9.
19. Yun J.W., Lee K.-O., Jung C.W., Oh S.-Y., Kim S.-H., Choi C.W., et al. Hereditary platelet function disorder from RASGRP2 gene mutations encoding CalDAG-GEFI identified by whole-exome sequencing in a Korean woman with severe bleeding. Haematologica 2019; 104 (6): e274–6.
20. Rosenberg N., Dardik R., Hauschner H., Nakav S., Barel O., Luboshitz J., et al. Mutations in RASGRP2 gene identified in patients misdiagnosed as Glanzmann thrombasthenia patients. Blood Cells Mol Dis 2021; 89: 102560.
Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 126-131
Hemorrhagic thrombocytopathy with defective signal transduction CalDAG-GEFI
https://doi.org/10.24287/1726-1708-2021-20-3-126-131Abstract
Hemorrhagic thrombocytopathy with defective signal transduction CalDAG-GEFI is a rare disease associated with a mutation in the RASGRP2 gene. At the moment, this disease is described in 10 person in the world. We present clinical case report of this pathology of a 9-year-old child. We also offer a review of the available literature about pathogenetic features, clinical manifestations and prevalence of this rare disease. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications.
References
1. McGarry G.W. Recurrent epistaxis in children. BMJ Clin Evid 2013; 2013: 0311.
2. Carpenter R.F. The prevalence and distribution of bruising in babies. Arch Dis Child 1999; 80: 363–6.
3. Collins P.W., Hamilton M., Dunstan F.D., Maguire S., Nuttall D.E., Liesner R., et al. Patterns of bruising in preschool children with inherited bleeding disorders: a longitudinal study. Arch Dis Child 2017; 102: 1110–7.
4. Downes A.J., Crossland D.S., Mellon A.F. Prevalence and distribution of petechiae in well babies. Arch Dis Child 2002; 86: 291–2.
5. Soheilifar J., Ahmadi M., Ahmadi M., Mobaien A.R. Prevalence and location of petechial spots in well infants. Arch Dis Child 2010; 95: 518–20.
6. Lambert M.P. Inherited Platelet Disorders: A Modern Approach to Evaluation and Treatment. Hematol Oncol Clin North Am 2019; 33 (3): 471–87. doi: 10.1016/j.hoc.2019.01.008
7. Fedorova D.V., Zharkov P.A., Ignatova A.A., Fedotov A.Yu., Polokhov D.M., Poletaev A.V. i dr. Diagnostika trombotsitopatii u detei: korrelyatsii issledovaniya funktsional'noi aktivnosti trombotsitov s klinicheskoi kartinoi i rezul'tatami agregometrii. Voprosy gematologii/onkologii i immunopatologii v pediatrii 2018; 17 (1): 16–22.
8. Svirin P.V., Ternavskii A.P., Vdovin V.V., Larina L.E., Razheva A.S., Livshits A.M. i dr. Rasprostranennost' gemorragicheskikh proyavlenii u moskovskikh detei shkol'nogo vozrasta. Pediatriya. Zhurnal im. G.N. Speranskogo 2011; 90 (4): 43–7.
9. Siddiq S., Clark A., Mumford A. Haemophilia. A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia. Available at: http://thrombo.cambridgednadiagnosis.org.uk/gene-disorder-list/. Accessed October 1, 2018.
10. Bowman M., Riddel J., Rand M.L., Tosetto A., Silva M., James P.D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire. J Thromb Haemost 2009; 7 (8): 1418–21.
11. Cifuni S.M., Wagner D.D., Bergmeier W. CalDAGGEFI and protein kinase C represent alternative pathways leading to activation of integrin aIIbb3 in platelets. Blood 2008; 112 (5): 1696–703.
12. Kawasaki H., Springett G.M., Toki S., Canales J.J., Harlan P., Blumenstiel J.P., et al. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A 1998; 95: 13278–83.
13. Crittenden J.R., Bergmeier W., Zhang Y., Piffath C.L., Liang Y., Wagner D.D., et al. CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nat Med 2004; 10 (9): 982–6.
14. Canault M., Ghalloussi D., Grosdidier C., Guinier M., Perret C., Chelghoum N., et al. Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding. J Exp Med 2014; 211 (7): 1349–62.
15. Lagarrigue F., Kim C., Ginsberg M.H. The Rap1-RIAMtalin axis of integrin activation and blood cell function. Blood 2016; 128 (4): 479–87.
16. Stefanini L., Paul D.S., Robledo R.F., Chan E.R., Getz T.M., Campbell R.A., et al. RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J Clin Invest 2015; 125 (4): 1419–32.
17. Cattaneo M. The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 2011; 117 (7): 2102– 12.
18. Lozano M.L., Cook A., Bastida J.M., Paul D.S., Iruin G., Cid A.R., et al. Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction. Blood 2016; 128 (9): 1282–9.
19. Yun J.W., Lee K.-O., Jung C.W., Oh S.-Y., Kim S.-H., Choi C.W., et al. Hereditary platelet function disorder from RASGRP2 gene mutations encoding CalDAG-GEFI identified by whole-exome sequencing in a Korean woman with severe bleeding. Haematologica 2019; 104 (6): e274–6.
20. Rosenberg N., Dardik R., Hauschner H., Nakav S., Barel O., Luboshitz J., et al. Mutations in RASGRP2 gene identified in patients misdiagnosed as Glanzmann thrombasthenia patients. Blood Cells Mol Dis 2021; 89: 102560.
