problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13713problendo-13713Research ArticleДетская эндокринологияPediatric EndocrinologyНормофосфатемический семейный опухолевый кальциноз: описание клинического случая с назначением гипофосфатемической терапииNormophosphatemic familial tumoral calcinosis: description of a case with phosphate lowering therapyhttps://orcid.org/0000-0001-5689-0194ВитебскаяА. В.VitebskayaA. V.

Витебская Алиса Витальевна, к.м.н., доцент

119435, Москва, ул. Большая Пироговская, д. 19, стр. 2

Alisa V. Vitebskaya, MD, PhD, Associate Professor

19-2 B.Pirogovskaya street, 119435 Moscow

dr.vitebskaya@mail.ruhttps://orcid.org/0000-0001-7747-6873ТихоновичЮ. В.TikhonovichYu. V.

Тихонович Юлия Викторовна, к.м.н. 

Москва

Yulia V. Tikhonovich, MD, PhD

Moscow

yuliatihonovich@mail.ruhttps://orcid.org/0000-0001-7736-5372КолодкинаА. А.KolodkinaA. A.

Колодкина Анна Александровна, к.м.н. 

Москва

Anna A. Kolodkina, MD, PhD

Moscow

anna_kolodkina@mail.ruПервый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияSechenov First Moscow State Medical UniversityRussian FederationПервый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет); Российский национальный исследовательский медицинский университет им. Н.И. Пирогова; Медико-генетический научный центр им. академика Н.П. БочковаРоссияSechenov First Moscow State Medical University; Russian National Research Medical University named after N.I. Pirogov; Medical Genetic Research Center named after Academician N.P. BochkovRussian FederationНациональный медицинский исследовательский центр эндокринологии им. академика И.И. ДедоваРоссияEndocrinology Research CenterRussian Federation2026080920267247079Copyright © Витебская А.В., Тихонович Ю.В., Колодкина А.А., 20262026Витебская А.В., Тихонович Ю.В., Колодкина А.А.Vitebskaya A.V., Tikhonovich Y.V., Kolodkina A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13713

Нормофосфатемический семейный опухолевый кальциноз (НСОК) характеризуется наличием кожных кальцинатов при отсутствии метаболических нарушений; манифестирует в первые годы жизни; ассоциирован с мутациями в гене SAMD9. В образовании кальцинатов ведущую роль играют хроническая травматизация и транзиторная гиперфосфатемия.

Хирургическое лечение позволяет избавляться от кальцинатов, но не предотвращает рецидивы и может приводить к осложнениям. Применяются различные методы консервативной терапии. Снижение уровня фосфатов в крови рассматривается как перспективный патогенетический метод лечения.

В статье представлен клинический случай пациента с НСОК, ассоциированный с гомозиготным вариантом p.E1200K в SAMD9. Особенностью нашего пациента является наличие множественных кальцинатов не только в местах травматизации (конечности), но и в местах угревой сыпи (лицо), а также особенно активное прогрессирование заболевания в период полового созревания. Уменьшение размеров кальцинатов отмечено на фоне 1 года постоянной гипофосфатемической терапии (гидроксид алюминия и севеламер 800 мг). Эффективность проводимой терапии дискутабельна, ограничена как плохой переносимостью севеламера пациентом, так и недостаточной приверженностью к лечению.

Это первое в России описание пациента с НСОК, подтвержденным молекулярно-генетически. Точная постановка диагноза позволила уточнить патогенетический механизм образования кальцинатов и предложить варианты терапии.

Normophosphatemic familial tumoral calcinosis (NFTC) is characterized by cutaneous calcifications with no metabolic disorders; it manifests in the first years of life; associated with mutations in SAMD9 gene. Chronic trauma and transient hyperphosphatemia play a leading role in calcification formation.

Surgical treatment can remove calcifications, but it does not prevent recurrence and can cause complications. Various conservative therapy is used. Lowering of blood phosphate levels is considered a promising pathogenetic treatment method.

We present a clinical case of a patient with NFTC associated with the homozygous variant p.E1200K in SAMD9. A characteristic feature of our patient is the presence of multiple calcifications not only in the areas of injury (limbs), but also in areas of acne (face), as well as particularly active progression of the disease during puberty. A reduction in calcification size was observed after one year of continuous hypophosphatemic therapy (aluminum hydroxide and sevelamer 800 mg). The effectiveness of this therapy is debatable and limited by both poor patient tolerability of sevelamer and poor adherence.

This is the first description of a patient with molecularly confirmed NFTC in Russia. A precise diagnosis allowed us to clarify the pathogenetic mechanism of calcification formation and propose treatment options.

нормофосфатемический семейный опухолевый кальцинозкальциноз кожиSAMD9севеламерnormophosphatemic familial tumoral calcinosiscalcinosis cutisSAMD9sevelamerReferencesElahmar H, Feldman BM, Johnson SR. Management of Calcinosis Cutis in Rheumatic Diseases. J Rheumatol. 2022 Sep;49(9):980-989. doi: https://doi.org/10.3899/jrheum.211393Elahmar H, Feldman BM, Johnson SR. Management of Calcinosis Cutis in Rheumatic Diseases. J Rheumatol. 2022 Sep;49(9):980-989. doi: https://doi.org/10.3899/jrheum.211393Fathi I, Sakr M. Review of tumoral calcinosis: A rare clinico pathological entity. World J Clin Cases. 20142(9):409-14. doi: https://doi.org/10.12998/wjcc.v2.i9.409Fathi I, Sakr M. Review of tumoral calcinosis: A rare clinico pathological entity. World J Clin Cases. 20142(9):409-14. doi: https://doi.org/10.12998/wjcc.v2.i9.409Smack D, Norton SA, Fitzpatrick JE. Proposal for a pathogenesis-based classification of tumoral calcinosis. Int J Dermatol. 1996;35(4):265-71. doi: https://doi.org/10.1111/j.1365-4362.1996.tb02999.xSmack D, Norton SA, Fitzpatrick JE. Proposal for a pathogenesis-based classification of tumoral calcinosis. Int J Dermatol. 1996;35(4):265-71. doi: https://doi.org/10.1111/j.1365-4362.1996.tb02999.xIchikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, et al. Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. Am J Med Genet A. 2010;152A(4):896-903. doi: https://doi.org/10.1002/ajmg.a.33337Ichikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, et al. Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. Am J Med Genet A. 2010;152A(4):896-903. doi: https://doi.org/10.1002/ajmg.a.33337Topaz O, Indelman M, Chefetz I, Geiger D, Metzker A, et al. A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis. Am J Hum Genet. 2006;79(4):759-64. doi: https://doi.org/10.1086/508069Topaz O, Indelman M, Chefetz I, Geiger D, Metzker A, et al. A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis. Am J Hum Genet. 2006;79(4):759-64. doi: https://doi.org/10.1086/508069Chefetz I, Ben Amitai D, Browning S, Skorecki K, Adir N, Thomas MG, et al. Normophosphatemic familial tumoral calcinosis is caused by deleterious mutations in SAMD9, encoding a TNF-alpha responsive protein. J Invest Dermatol. 2008;128(6):1423-9. doi: https://doi.org/10.1038/sj.jid.5701203Chefetz I, Ben Amitai D, Browning S, Skorecki K, Adir N, Thomas MG, et al. Normophosphatemic familial tumoral calcinosis is caused by deleterious mutations in SAMD9, encoding a TNF-alpha responsive protein. J Invest Dermatol. 2008;128(6):1423-9. doi: https://doi.org/10.1038/sj.jid.5701203Leow MKS, Ang J, Bi X, Koh ET, McFarlane C. Alterations in SAMD9, AHSG, FRG2C, and FGFR4 Genes in a Case of Late-Onset Massive Tumoral Calcinosis. AACE Clin Case Rep. 2023;9(5):153-157. doi: https://doi.org/10.1016/j.aace.2023.05.004Leow MKS, Ang J, Bi X, Koh ET, McFarlane C. Alterations in SAMD9, AHSG, FRG2C, and FGFR4 Genes in a Case of Late-Onset Massive Tumoral Calcinosis. AACE Clin Case Rep. 2023;9(5):153-157. doi: https://doi.org/10.1016/j.aace.2023.05.004Mehawej C, Ibrahim M, Khalife L, Chouery E, El Hachem S, et al. A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects. Clin Genet. 2024;105(2):202-208. doi: https://doi.org/10.1111/cge.14439Mehawej C, Ibrahim M, Khalife L, Chouery E, El Hachem S, et al. A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects. Clin Genet. 2024;105(2):202-208. doi: https://doi.org/10.1111/cge.14439Аведова А.Я. и соавт. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. — 2022. — Т.21. — №3. — С.126–135. doi: https://doi.org/10.24287/1726-1708-2022-21-3-126-135Avedova AYa, et al. Pediatric Hematology/ Oncology and Immunopathology. 2022;21(3):126–135. (in Russ.) doi: https://doi.org/10.24287/1726-1708-2022-21-3-126-135Zuo QY, Cao X, Liu BY, et al. Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients. J Endocrinol Invest. 2020;43:173–183. doi: https://doi.org/10.1007/s40618-019-01097-4Zuo QY, Cao X, Liu BY, et al. Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients. J Endocrinol Invest. 2020;43:173–183. doi: https://doi.org/10.1007/s40618-019-01097-4Anilkumar A, Högler W, Bursell J, Nadar R, Ryan F, et al. Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis. Bone. 2024;182:117049. doi: https://doi.org/10.1016/j.bone.2024.117049Anilkumar A, Högler W, Bursell J, Nadar R, Ryan F, et al. Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis. Bone. 2024;182:117049. doi: https://doi.org/10.1016/j.bone.2024.117049Motlaghzadeh Y, Tabatabai LS, Longo E, Sellmeyer DE. Regression of calcinosis cutis after inkless tattoo in a patient with dermatomyositis: therapeutic potential of microneedling. Osteoporos Int. 2022;33(11):2449-2452. doi: https://doi.org/10.1007/s00198-022-06501-zMotlaghzadeh Y, Tabatabai LS, Longo E, Sellmeyer DE. Regression of calcinosis cutis after inkless tattoo in a patient with dermatomyositis: therapeutic potential of microneedling. Osteoporos Int. 2022;33(11):2449-2452. doi: https://doi.org/10.1007/s00198-022-06501-zGiuggioli D, Lumetti F, Spinella A, et al. Use of Neem oil and Hypericum perforatum for treatment of calcinosis-related skin ulcers in systemic sclerosis. J Int Med Res 2020;48:300060519882176Giuggioli D, Lumetti F, Spinella A, et al. Use of Neem oil and Hypericum perforatum for treatment of calcinosis-related skin ulcers in systemic sclerosis. J Int Med Res 2020;48:300060519882176López-Sundh AE, Quintana-Sancho A, Durán-Vian C, Reguero-DelCura L, Corrales-Martínez AF, et al. Clinical and ultrasound response to intralesional sodium thiosulfate for the treatment of calcinosis cutis in the setting of systemic sclerosis. A case-based review. Clin Rheumatol. doi: https://doi.org/10.1007/s10067-020-05523-4López-Sundh AE, Quintana-Sancho A, Durán-Vian C, Reguero-DelCura L, Corrales-Martínez AF, et al. Clinical and ultrasound response to intralesional sodium thiosulfate for the treatment of calcinosis cutis in the setting of systemic sclerosis. A case-based review. Clin Rheumatol. doi: https://doi.org/10.1007/s10067-020-05523-4Tubau C, Cubiró X, Amat-Samaranch V, Garcia-Melendo C, Puig L, Roé-Crespo E. Clinical and ultrasonography follow up of five cases of calcinosis cutis successfully treated with intralesional sodium thiosulfate. J Ultrasound. 2022;25(4):995-1003. doi: https://doi.org/10.1007/s40477-022-00665-4Tubau C, Cubiró X, Amat-Samaranch V, Garcia-Melendo C, Puig L, Roé-Crespo E. Clinical and ultrasonography follow up of five cases of calcinosis cutis successfully treated with intralesional sodium thiosulfate. J Ultrasound. 2022;25(4):995-1003. doi: https://doi.org/10.1007/s40477-022-00665-4Nowaczyk J, Zawistowski M, Fiedor P. Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review. Arch Dermatol Res. 2022;314(6):515-525. doi: https://doi.org/10.1007/s00403-021-02264-5Nowaczyk J, Zawistowski M, Fiedor P. Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review. Arch Dermatol Res. 2022;314(6):515-525. doi: https://doi.org/10.1007/s00403-021-02264-5Chung MP, Valenzuela A, Li S, et al. A pilot study to evaluate the safety and efficacy of treprostinil in the treatment of calcinosis in systemic sclerosis. Rheumatology. 2022;61:2441-9Chung MP, Valenzuela A, Li S, et al. A pilot study to evaluate the safety and efficacy of treprostinil in the treatment of calcinosis in systemic sclerosis. Rheumatology. 2022;61:2441-9Rauch L, Hein R, Biedermann T, Eyerich K, Lauffer F. Bisphosphonates for the Treatment of Calcinosis Cutis—A Retrospective Single-Center Study. Biomedicines. 2021;9:1698. doi: https://doi.org/10.3390/biomedicines9111698Rauch L, Hein R, Biedermann T, Eyerich K, Lauffer F. Bisphosphonates for the Treatment of Calcinosis Cutis—A Retrospective Single-Center Study. Biomedicines. 2021;9:1698. doi: https://doi.org/10.3390/biomedicines9111698Soumya S, Prasad N, Jabbar PK, Hussain S, Jayakumari C, Nair A. Beneficial Response to Phosphate Lowering Therapy in Normophosphatemic Tumoral Calcinosis. Indian Pediatr. 2021;58(1):88-89. doi: https://doi.org/10.1007/s13312-021-2109-6Soumya S, Prasad N, Jabbar PK, Hussain S, Jayakumari C, Nair A. Beneficial Response to Phosphate Lowering Therapy in Normophosphatemic Tumoral Calcinosis. Indian Pediatr. 2021;58(1):88-89. doi: https://doi.org/10.1007/s13312-021-2109-6Инструкция к препарату севеламер https://www.vidal.ru/drugs/molecule/1893, запрос 29.12.2025Instructions for the drug Sevelamer https://www.vidal.ru/drugs/molecule/1893, request 12/29/2025 (in Russ.)

The authors declare that there are no conflicts of interest present.