Атипичное осложненное течение IPEX-синдрома у ребенка грудного возраста (клинический случай): КЛИНИЧЕСКИЙ СЛУЧАЙ

Евгения Анатольевна  Рябова; Марина Вячеславовна  Белянская; Руслан Магомедович  Абисов; Владимир Максимович  Менжулов; Михаил Александрович  Сидненко; Наталья Борисовна  Юдина; Элиза Газинуровна  Аббасова

doi:10.56871/PED.2026.20.11.011

Atypical complicated course of IPEX syndrome in infant (clinical case)

CLINICAL CASE

Evgeniya A. Ryabova Voronezh Regional Children’s Clinical Hospital No. 1 https://orcid.org/0000-0001-5731-7242
Marina V. Belyanskaya Voronezh Regional Children’s Clinical Hospital No. 1 https://orcid.org/0000-0002-1947-0278
Ruslan M. Abisov Voronezh Regional Children’s Clinical Hospital No. 1; Voronezh State Medical University named after N.N. Burdenko https://orcid.org/0009-0009-3398-1697
Vladimir M. Menzhulov Voronezh State Medical University named after N.N. Burdenko https://orcid.org/0009-0001-5378-8589
Mikhail A. Sidnenko Voronezh Regional Children’s Clinical Hospital No. 1 https://orcid.org/0009-0001-2720-923X
Natalia B. Yudina Voronezh Regional Children’s Clinical Hospital No. 1 https://orcid.org/0009-0001-7498-0836
Eliza G. Abbasova Voronezh State Medical University named after N.N. Burdenko https://orcid.org/0009-0003-6451-8853

Keywords:

IPEX syndrome Fisher–Evans syndrome autoimmune hemolytic anemia cytomegalovirus pneumonia acute respiratory distress syndrome pediatric IPEX-синдром синдром Фишера–Эванса аутоиммунная гемолитическая анемия цитомегаловирусная пневмония острый респираторный дистресс-синдром дети

Abstract

IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) is an extremely rare autoimmune disease caused by a mutation of the FOXP3 gene, characterized by immunodeficiency and pronounced phenotypic variability, which complicates the timely diagnosis and treatment of patients. The features of the complicated course of IPEX syndrome in infants. Since birth, the patient has had recurrent hemolytic crises of autoimmune origin. At the age of nine months, severe cytomegalovirus pneumonia developed, complicated by severe acute respiratory distress syndrome and sepsis, which required prolonged respiratory support. The patient received immunosuppressive and antibacterial therapy with a positive effect, stabilization of the condition was achieved, and allogeneic hematopoietic stem cell transplantation is planned. Based on a molecular genetic study, a variant in the FOXP3 gene c .227dcl, p. (L76Qfs*53) in a hemizygous state was identified. A similar variant in the heterozygous state was found in the patient’s mother. No variants were found during Sanger sequencing of the FOXP3 gene of the patient’s older brother. The younger brother has a variant in the FOXP3 gene c.227dcl, p. (L76Qfs*53) in a hemizygous state. A distinctive feature of the presented case was the absence of polyendocrinopathy and the dominance of autoimmune cytopenia (B-cell lymphopenia, NK-cell cytopenia) over the symptoms of enteropathy. This case highlights the need to include IPEX syndrome in the differential diagnostic series in patients with autoimmune cytopenia, enteropathy, and severe opportunistic infections, even in the absence of classical polyendocrinopathy. The earliest possible genome-wide sequencing and timely radical treatment (alloimmune hematopoietic stem cell transplantation) are critically important for improving the outcome of this disease.

Author Biographies

Evgeniya A. Ryabova, Voronezh Regional Children’s Clinical Hospital No. 1

Ph D, hematologist, pediatric oncologist of the Oncohematology Chemotherapy Department, Voronezh Regional Children’s Clinical Hospital No. 1; address: 114/49 Lomonosova str., Voronezh, 394087, Russia

Marina V. Belyanskaya, Voronezh Regional Children’s Clinical Hospital No. 1

hematologist, pediatric oncologist of the Oncohematology С hemotherapy Department, Voronezh Regional Children’s Clinical Hospital No. 1, Voronezh, Russia

Ruslan M. Abisov, Voronezh Regional Children’s Clinical Hospital No. 1; Voronezh State Medical University named after N.N. Burdenko

anesthesiologist and intensive care physician, Head of the Department of Resuscitation and Intensive Care, Voronezh Regional Children’s Clinical Hospital No. 1, Voronezh, Russia; Assistant, Department of Anesthesiology and Intensive Care, Voronezh State Medical University named after N.N. Burdenko, Voronezh, Russia

Vladimir M. Menzhulov, Voronezh State Medical University named after N.N. Burdenko

6thyear medical student, Voronezh State Medical University named after N.N. Burdenko, Voronezh, Russia

Mikhail A. Sidnenko, Voronezh Regional Children’s Clinical Hospital No. 1

anesthesiologist and intensive care physician of the Department of Resuscitation and Intensive Care, hematologist, Voronezh Regional Children’s Clinical Hospital No. 1, Voronezh, Russia

Natalia B. Yudina, Voronezh Regional Children’s Clinical Hospital No. 1

hematologist, pediatric oncologist, Head of the Oncohematology Department, Voronezh Regional Children’s Clinical Hospital No. 1, Voronezh, Russia

Eliza G. Abbasova, Voronezh State Medical University named after N.N. Burdenko

6thyear medical student, Voronezh State Medical University named after N.N. Burdenko, Voronezh, Russia

References

1. Barzaghi F., Passerini L. IPEX Syndrome: improved knowledge of immune pathogenesis empowers diagnosis. Front Pediatr. 2021;9:612760. https://doi.org/10.3389/fped.2021.612760.

2. Ben-Skowronek I. IPEX Syndrome: genetics and treatment options. Genes (Basel). 2021;12(3):323. https://doi.org/10.3390/genes12030323.

3. Gambineri E., Ciullini Mannurita S., Hagin D. et al. Clinical, immunological, and molecular heterogeneity of 173 patients with the phenotype of immune dysregulation, polyendocrinopathy, enteropathy, x-linked (IPEX) syndrome. Front Immunol. 2018;9:2411. https://doi.org/10.3389/fimmu.2018.02411.

4. Miano M. How I manage Evans syndrome and AIHA cases in children. Br J Haematol. 2016;172(4):524–534. https://doi.org/10.1111/bjh.13866.

5. Powell B.R., Buist N.R., Stenzel P. An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr. 1982;100(5):731–737. https://doi.org/10.1016/s0022-3476(82)80573-8.

6. Тихонович Ю.В., Петряйкина Е.Е., Рыбкина И.Г. и др. Х-сцепленные иммунная дисрегуляция, полиэндокринопатия и энтеропатия (IPEX-синдром): описание клинического случая и краткий обзор литературы. Проблемы эндокринологии. 2014;60(5):55–61. https://doi.org/10.14341/probl201460529-33.

7. Zama D., Cocchi I., Masetti R. et al. Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, Х-linked syndrome (IPEX) with intractable diarrhea. Ital J Pediatr. 2014;40:68. https://doi.org/10.1186/s13052-014-0068-4.

8. Туркунова М.Е., Дитковская Л.В., Суспицын Е.Н. и др. Неонатальный сахарный диабет в структуре IPEX-синдрома. Педиатр. 2017;8(2):99–104.

9. Yaz I., Oskay Halacli S., Ipsir C. et al. Beyond the classical triad: atypical presentations and regulatory t cell phenotyping in a cohort of IPEX patients. J Clin Immunol. 2025;45(1):148. https://doi.org/10.1007/s10875-025-01934-7.

10. Tan Q.K.G., Louie R.J., Sleasman J.W. IPEX Syndrome. In: Adam M.P., Feldman J., Mirzaa G.M., Pagon R.A., Wallace S.E., Amemiya A., editors. Gene Reviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2004.

11. Wildin R.S., Smyk-Pearson S., Filipovich A.H. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002;39(8):537–545. https://doi.org/10.1136/jmg.39.8.537.

12. Шабашова Н.В., Филиппова Л.В., Учеваткина А.Е., Фролова Е.В. Общая вариабельная иммунная недостаточность у взрослых. Терапевтический архив. 2016;88(11):116–121. https://doi.org/10.17116/terarkh2016881194-98.

13. Ye L., Song X., Cui Y. et al. Sirolimus alleviated intractable diarrhea of IPEX syndrome: a case report and literature review. BMC Pediatr. 2024;24(1):806. https://doi.org/10.1186/s12887-024-05264-2.

14. Ковынев И.Б., Поспелова Т.И., Мишенин А.В. и др. Аутоиммунный лимфопролиферативный синдром в гематологической клинике: обзор литературы и собственное наблюдение. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2013;6(2):195–203. EDN: SZHULD.

15. Brunkow M.E., Jeffery E.W., Hjerrild K.A. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nature Genetics. 2001;27(1):68–73. https://doi.org/10.1038/83784.

16. Despotovic J.M. Immune hematology: diagnosis and management of autoimmune cytopenias. Springer; 2018. 311 p.

17. Александрович Ю.С., Пшениснов К.В., Колодяжная В.И. Острый респираторный дистресс-синдром в педиатрической практике: диагностика и интенсивная терапия. Обзор литературы. Российский вестник детской хирургии, анестезиологии и реаниматологии. 2024;14(1):83–95. https://doi.org/10.17816/psaic1569.

18. Gambineri E., Ciullini Mannurita S., Hagin D. et al. Clinical, immunological, and molecular heterogeneity of 173 patients with the phenotype of immune dysregulation, polyendocrinopathy, enteropathy, x-linked (IPEX) Syndrome. Front Immunol. 2018;9:2411. https://doi.org/10.3389/fimmu.2018.02411.

19. Kobayashi I., Shiari R., Yamada M. et al. Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX). J Med Genet. 2001;38(12):874–876. https://doi.org/10.1136/jmg.38.12.874.