perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2022-67-4-137-142perinatology-1686Research ArticleВ ПОМОЩЬ ПРАКТИЧЕСКОМУ ВРАЧУFOR THE PRACTITIONERВитамин D-зависимый рахит 1А типаVitamin D-dependent rickets type 1Ahttps://orcid.org/0000-0001-9836-6841ПотроховаЕ. А.PotrokhovaE. A.

 д.м.н., проф., зав. педиатрическим отделением, вед. науч. сотр. отдела радиационной экопатологии детского возраста, 

125412 Москва, ул. Талдомская, д. 2

Moscow

potrokhova@pedklin.ruhttps://orcid.org/0000-0001-9914-0123БалеваЛ. С.BalevaL. S.

д.м.н., проф., рук. научного отдела радиационной экопатологии детского возраста,

125412 Москва, ул. Талдомская, д. 2

Moscow

https://orcid.org/0000-0001-9779-9899СафоноваМ. П.SafonovaM. P.

к.м.н., врач-педиатр педиатрического отделения, вед. науч. сотр. отдела радиационной экопатологии детского возраста, 

125412 Москва, ул. Талдомская, д. 2

Moscow

https://orcid.org/0000-0001-7728-7984СипягинаА. Е.SipyaginaA. E.

д.м.н., гл. науч. сотр. отдела радиационной экопатологии детского возраста,

125412 Москва, ул. Талдомская, д. 2

Moscow

ОСП «Научно-исследовательский клинический институт педиатрии им. академика Ю.Е. Вельтищева» ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical UniversityRussian Federation202222092022674137142Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20222022Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1686

Витамин D-зависимый рахит 1А типа — редкое аутосомно-рецессивное заболевание, вызванное мутацией гена CYP27B1, приводящей к снижению активности фермента 1-альфа-гидроксилазы и нарушению метаболизма витамина D. Клинически заболевание проявляется рахитическими изменениями, не отличающимися от симптомов витамин D-дефицитного рахита, что затрудняет раннюю диагностику болезни и своевременное назначение адекватной патогенетической терапии с использованием активных метаболитов витамина D. В обзоре представлены вопросы этиологии, патогенеза, диагностики, дифференциальной диагностики, лечения витамин D-зависимого рахита 1А типа и на примере клинического случая показаны принципы подбора адекватной дозы заместительной терапии. 

Vitamin D-dependent rickets type 1 is a rare autosomal recessive disorder caused by mutation of the CYP27B1 gene, that further leads to a decrease in the activity of 1A-hydroxylase and vitamin D metabolic disorder. The disease manifests itself by means of rickets-like changes, alike to the symptoms of vitamin D-deficiency rickets, what inhibits both the early diagnosis and timely appointment of an adequate pathogenetic therapy with the usage of active vitamin D metabolites. Etiology, pathogenesis, diagnosis, differential diagnosis, and treatment of vitamin D-dependent rickets type 1A issues are presented in this article. Using the example of the clinical case, it shows the principles of selecting an adequate dose of replacement therapy. 

детирахитоподобное заболеваниевитамин D-зависимый рахитген CYP27B11α-гидроксилазакальцитриолклинический случайобзорchildrenrickets-like diseasevitamin D-dependent ricketsCYP27B1 gene1α-hydroxylasecalcitriolclinical casereviewReferencesLevine M.A. Diagnosis and management of vitamin D dependent rickets. Front Pediatr 2020; 8: 315. DOI: 10.3389/fped.2020.00315Levine M.A. Diagnosis and management of vitamin D dependent rickets. Front Pediatr 2020; 8: 315. DOI: 10.3389/fped.2020.00315Fraser D., Salter R.B. The diagnosis and management of the various types of rickets. Pediatric Clinics of North America 1958; 5: 417-441. DOI: 10.1016/S0031-3955(16)30659-9Fraser D., Salter R.B. The diagnosis and management of the various types of rickets. Pediatric Clinics of North America 1958; 5: 417-441. DOI: 10.1016/S0031-3955(16)30659-9Prader A., Illig R., Heierli E. Eine besondere Form der primaren vitamin-D-resistenten Rachitis mit Hypocalcamie und autosomal-dominantem Erbgang: Die hereditare Pseudo-mangelrachitis. Helv Paediat Acta 1961; 16: 452-468Prader A., Illig R., Heierli E. Eine besondere Form der primaren vitamin-D-resistenten Rachitis mit Hypocalcamie und autosomal-dominantem Erbgang: Die hereditare Pseudo-mangelrachitis. Helv Paediat Acta 1961; 16: 452-468Fraser D., Kooh S.W., Kind H.P., Holick M.F., Tanaka Y., DeLuca H.F. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N Engl J Med 1973; 289: 817- 822. DOI: 10.1056/NEJM197310182891601Fraser D., Kooh S.W., Kind H.P., Holick M.F., Tanaka Y., DeLuca H.F. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N Engl J Med 1973; 289: 817- 822. DOI: 10.1056/NEJM197310182891601Fu G.K., Lin D., Zhang M.Y., Bikle D.D., Shackleton C.H., Miller W.L. et al. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol 1997; 11: 1961-1970. DOI: 10.1210/mend.11.13.0035Fu G.K., Lin D., Zhang M.Y., Bikle D.D., Shackleton C.H., Miller W.L. et al. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol 1997; 11: 1961-1970. DOI: 10.1210/mend.11.13.0035Shinki T., Shimada H., Wakino S., Anazawa H., Hayashi M., Saruta T. et al. Cloning and expression of rat 25-hydroxyvitamin D3 -1-alpha-hydroxylase cDNA. Proc Natl Acad Sci USA 1997; 94: 12920-12925. DOI: 10.1073/pnas.94.24.12920Shinki T., Shimada H., Wakino S., Anazawa H., Hayashi M., Saruta T. et al. Cloning and expression of rat 25-hydroxyvitamin D3 -1-alpha-hydroxylase cDNA. Proc Natl Acad Sci USA 1997; 94: 12920-12925. DOI: 10.1073/pnas.94.24.12920St-Arnaud R., Messerlian S., Moir J.M., Omdahl J.L., Glorieux F.H. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res 1997; 12: 1552- 1559. DOI: 10.1359/jbmr.1997.12.10.1552St-Arnaud R., Messerlian S., Moir J.M., Omdahl J.L., Glorieux F.H. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res 1997; 12: 1552- 1559. DOI: 10.1359/jbmr.1997.12.10.1552Takeyama K., Kitanaka S., Sato T., Kobori M., Yanagisawa J., Kato S. 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science 1997; 277: 1827-1830. DOI: 10.1126/science.277.5333.1827Takeyama K., Kitanaka S., Sato T., Kobori M., Yanagisawa J., Kato S. 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science 1997; 277: 1827-1830. DOI: 10.1126/science.277.5333.1827Bland R., Walker E.A., Hughes S.V., Stewart P.M., Hewison M. Constitutive expression of 25-hydroxyvitamin D3-1a-hydroxylase in a transformed human proximal tubule cell line: Evidence for direct regulation of vitamin D metabolism by calcium. Endocrinology 1999; 140: 2027-2034. DOI: 10.1210/endo.140.5.6683Bland R., Walker E.A., Hughes S.V., Stewart P.M., Hewison M. Constitutive expression of 25-hydroxyvitamin D3-1a-hydroxylase in a transformed human proximal tubule cell line: Evidence for direct regulation of vitamin D metabolism by calcium. Endocrinology 1999; 140: 2027-2034. DOI: 10.1210/endo.140.5.6683De Braekeleer M. Hereditary disorders in Saguenay-LacSt-Jean (Quebec, Canada). Hum Hered 1991; 41:141-146. DOI: 10.1159/000153992De Braekeleer M. Hereditary disorders in Saguenay-LacSt-Jean (Quebec, Canada). Hum Hered 1991; 41:141-146. DOI: 10.1159/000153992Miller W.L. Genetic disorders of Vitamin D biosynthesis and degradation. J Steroid Biochem Mol Biol 2017; 165: 101- 108. DOI: 10.1016/j.jsbmb.2016.04.001Miller W.L. Genetic disorders of Vitamin D biosynthesis and degradation. J Steroid Biochem Mol Biol 2017; 165: 101- 108. DOI: 10.1016/j.jsbmb.2016.04.001Labuda M., Morgan K., Glorieux F.H. Mapping autosomal recessive vitamin D dependency type 1 to chromosomal 12q14 by linkage analysis. Am J Hum Genet 1990; 47: 28-36Labuda M., Morgan K., Glorieux F.H. Mapping autosomal recessive vitamin D dependency type 1 to chromosomal 12q14 by linkage analysis. Am J Hum Genet 1990; 47: 28-36The Human Gene Mutation Database. Version HGMD Professional 2017.4. https://portal.biobase-international.comThe Human Gene Mutation Database. Version HGMD Professional 2017.4. https://portal.biobase-international.comTrochoutsou A.I., Kloukina V., Samitas K., Xanthou G. Vitamin-D in the Immune System: Genomic and Non-Genomic Actions. Mini Rev Med Chem 2015; 15(11): 953-963. DOI: 10.2174/1389557515666150519110830Trochoutsou A.I., Kloukina V., Samitas K., Xanthou G. Vitamin-D in the Immune System: Genomic and Non-Genomic Actions. Mini Rev Med Chem 2015; 15(11): 953-963. DOI: 10.2174/1389557515666150519110830Martens P.J., Gysemans C., Verstuyf A., Mathieu A.C. Vitamin D’s Effect on Immune Function. Nutrients 2020; 12(5): 1248. DOI: 10.3390/nu12051248Martens P.J., Gysemans C., Verstuyf A., Mathieu A.C. Vitamin D’s Effect on Immune Function. Nutrients 2020; 12(5): 1248. DOI: 10.3390/nu12051248Carlberg C., Velleuer E. Vitamin D and the risk for cancer: A molecular analysis. Biochem Pharmacol 2022; 196: 114735. DOI: 10.1016/j.bcp.2021.114735Carlberg C., Velleuer E. Vitamin D and the risk for cancer: A molecular analysis. Biochem Pharmacol 2022; 196: 114735. DOI: 10.1016/j.bcp.2021.114735Pike J.W., Christakos S. Biology and Mechanisms of Action of the Vitamin D Hormone. Endocrinol Metab Clin North Am 2017; 46(4): 815-843. DOI: 10.1016/j.ecl.2017.07.001Pike J.W., Christakos S. Biology and Mechanisms of Action of the Vitamin D Hormone. Endocrinol Metab Clin North Am 2017; 46(4): 815-843. DOI: 10.1016/j.ecl.2017.07.001Acar S., Demir K., Shi Y. Genetic Causes of Rickets. J Clin Res Pediatr Endocrinol 2017; 9 (Suppl 2): 88-105. DOI: 10.4274/jcrpe.2017.S008Acar S., Demir K., Shi Y. Genetic Causes of Rickets. J Clin Res Pediatr Endocrinol 2017; 9 (Suppl 2): 88-105. DOI: 10.4274/jcrpe.2017.S008Nemer P., Sinha R., Nemer L., Krishnappa V., Sochett E. et al. An overview of rickets in children Kidney. Int Rep 2020; 5(7): 980-990. DOI: 10.1016/j.ekir.2020.03.025Nemer P., Sinha R., Nemer L., Krishnappa V., Sochett E. et al. An overview of rickets in children Kidney. Int Rep 2020; 5(7): 980-990. DOI: 10.1016/j.ekir.2020.03.025Roizen J.D., Li D., O’Lear L., Javaid M.K., Shaw N.J., Ebeling P.R. et al. CYP3A4 mutation causes vitamin D-dependent rickets type 3. J Clin Invest 2018; 128: 1913-1918. DOI: 10.1172/JCI98680Roizen J.D., Li D., O’Lear L., Javaid M.K., Shaw N.J., Ebeling P.R. et al. CYP3A4 mutation causes vitamin D-dependent rickets type 3. J Clin Invest 2018; 128: 1913-1918. DOI: 10.1172/JCI98680Schirmer M., Toliat M.R., Haberl M., Suk A., Kamdem L.K., Klein K. et al. Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations. Pharmacogenetics Genomics 2006; 16: 59-71. DOI: 10.1097/01.fpc.0000182779.03180.baSchirmer M., Toliat M.R., Haberl M., Suk A., Kamdem L.K., Klein K. et al. Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations. Pharmacogenetics Genomics 2006; 16: 59-71. DOI: 10.1097/01.fpc.0000182779.03180.baНациональная программа «Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции». Союз педиатров России и др. М.: ПедиатрЪ, 2018: 96.National program «Vitamin D deficiency in children and adolescents of the Russian Federation: modern approaches to correction». M.: Pediatr, 2018: 96 s. (in Russ.)Root A.W., Diamond F.B. Disorders of mineral homeostasis in children and adolescents. In: Sperling M, editor. Pediatric Endocrinology Vol 4th edition. Philadelphia: Saunders-Elsevier; 2014: 734-845Root A.W., Diamond F.B. Disorders of mineral homeostasis in children and adolescents. In: Sperling M, editor. Pediatric Endocrinology Vol 4th edition. Philadelphia: Saunders-Elsevier; 2014: 734-845Baştuğ F., Gündüz Z., Tülpar S., Poyrazoğlu H., Düşünsel R. Urolithiasis in infants: evaluation of risk factors. World J Urol 2013; 31: 1117-1122. DOI: 10.1007/s00345-012-0828-yBaştuğ F., Gündüz Z., Tülpar S., Poyrazoğlu H., Düşünsel R. Urolithiasis in infants: evaluation of risk factors. World J Urol 2013; 31: 1117-1122. DOI: 10.1007/s00345-012-0828-yTiosano D., Hadad S., Chen Z., Nemirovsky A., Gepstein V., Militianu D. et al. Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets. J Clin Endocrinol Metab 2011; 96: 3701-3709Tiosano D., Hadad S., Chen Z., Nemirovsky A., Gepstein V., Militianu D. et al. Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets. J Clin Endocrinol Metab 2011; 96: 3701-3709Malloy P.J., Feldman D. Genetic disorders and defects in vitamin D action. Rheum Dis Clin North Am 2012; 38(1): 93- 106. DOI: 10.1016/j.rdc.2012.03.009Malloy P.J., Feldman D. Genetic disorders and defects in vitamin D action. Rheum Dis Clin North Am 2012; 38(1): 93- 106. DOI: 10.1016/j.rdc.2012.03.009Damiani F.M., Martin R.M., Latronico A.C., Ferraz-de-Souza B. Normal bone mass and normocalcemia in adulthood despite homozygous vitamin D receptor mutations. Osteoporos Int 2015; 26(6): 1819-1823. DOI: 10.1007/s00198-015-3076-3Damiani F.M., Martin R.M., Latronico A.C., Ferraz-de-Souza B. Normal bone mass and normocalcemia in adulthood despite homozygous vitamin D receptor mutations. Osteoporos Int 2015; 26(6): 1819-1823. DOI: 10.1007/s00198-015-3076-3Durmaz E., Zou M., Al-Rijjal R.A., Bircan I., Akçurin S., Meyer B., Shi Y. Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. Clin Endocrinol 2012; 77: 363-369. DOI: 10.1111/j.1365-2265.2012.04394.xDurmaz E., Zou M., Al-Rijjal R.A., Bircan I., Akçurin S., Meyer B., Shi Y. Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. Clin Endocrinol 2012; 77: 363-369. DOI: 10.1111/j.1365-2265.2012.04394.x

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