Генерализованная артериальная кальцификация у младенцев вследствие мутации генов ENPP1, ABCC6: особенности фенотипа, терапия бисфосфонатами

В обзоре литературы отражены современные представления о патогенезе, особенностях фенотипа, течения и прогноза редкой (орфанной) болезни — генерализованной артериальной кальцификации у младенцев 1-го типа вследствие мутации гена ENPP1 и 2-го типа вследствие мутации гена ABCC6. Опубликованные результаты клинических наблюдений подтвердили эффективность терапии бисфосфонатами у педиатрических пациентов с генерализованной артериальной кальцификацией 2-го типа. Заместительная ферментная терапия рекомбинантным ENPP1, которая может предотвратить артериальную кальцификацию и пролиферацию интимы, снизить артериальную гипертензию и смертность в эксперименте на мышиных моделях дефицита ENPP1, является перспективной.

1. OMIM. https://www.omim.org/entry/208000?search=Arterial%20calcification%20generalized% 20of%20infancy&highlight=%28generalised%7Cgeneralized%29%20arterial%20calcification%20infancy%20of. / Активна на 11.11.2023

2. https://www.omim.org/entry/614473?search=Arterial%20calcification%20generalized%20of%20infancy&highlight=%28generalised%7Cgeneralized%29%20arterial%20 calcification%20infancy%20of. / Активна на 11.12.2023

3. ORPHA. https://www.orpha.net/consor/cgi-bin/Disease_Classif_Simple.php?lng=EN / Активна на 11.11.2023

4. Ferreira C.R., Kintzinger K., Hackbarth M.E., Botschen U., Nitschke Y., Mughal M.Z. et al. Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies. J Bone Miner Res 2021; 36(11): 2193– 2202. DOI: 10.1002/jbmr.4418

5. Zimmerman K., Liu X., von Kroge S., Stabach P., Lester E.R., Chu E.Y. et al. Catalysis-Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass. J Bone Miner Res 2022;37(9):1733–1749. DOI: 10.1002/jbmr.4640

6. Shimada B.K., Pomozi V., Zoll J., Kuo S., Martin L., Le Saux O. ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions. Int J Mol Sci 2021; 22(9): 4555. DOI: 10.3390/ijms22094555

7. Boyce A.M., Gafni R.I., Ferreira C.R. Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management. Curr Osteoporos Rep 2020; 18(3): 232–241. DOI: 10.1007/s11914-020-00577-4

8. Pu L., Dai X., Liu H., Li L., Zhao F., Chen J. Prenatal diagnosis of generalized arterial calcification of infancy in the second trimester. Prenat Diagn 2022; 42(12): 1538–1544. DOI: 10.1002/pd.6245

9. Hailu S.S., Derbew H.M., Hailemeriam T. Generalized arterial calcification of infancy in a neonate with acute kidney injury: A rare case report. Radiol Case Rep 2023; 18(10): 3376–3379. DOI: 10.1016/j.radcr.2023.07.019

10. Rutsch F., Böyer P., Nitschke Y., Ruf N., Lorenz-Depierieux B., Wittkampf T. et al. GACI Study Group. Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circulation: Cardiovasc Genet 2008; 1(2): 133–140. DOI: 10.1161/CIRCGENETICS.108.797704

11. Lorenz-Depiereux B., Schnabel D., Tiosano D., Häusler G., Strom T.M. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet 2010; 12;86(2) :267–272. DOI: 10.1016/j.ajhg.2010.01.006

12. Lu P., Chen J., Chen M., Wang L., Xiang D., Yin J. et al. Case report: A rare homozygous variation in the ENPP1 gene, presenting with generalized arterial calcification of infancy in a Chinese infant. Front Cardiovasc Med 2023; 10: 1105381. DOI: 10.3389/fcvm.2023.1105381

13. Grosyeux C., Jourdan L., Jellimann J.M., Grandmougin A., Bronner M., Lambert L. et al. ENPP1 homozygous stop-loss variant causing generalized arterial calcifications of infancy: About a severe neonatal clinical case. Eur J Med Genet 2023; 66(8): 104803. DOI: 10.1016/j.ejmg.2023.104803

14. Mercurio S.A., Chunn L.M., Khursigara G., Nester C., Wray K., Botschen U. et al. ENPP1 deficiency: A clinical update on the relevance of individual variants using a locusspecific patient database. Hum Mutat 2022; 43(12): 1673– 1705. DOI: 10.1002/humu.24477

15. Chunn L.M., Bissonnette J., Heinrich S.V., Mercurio S.A., Kiel M.J., Rutsch F. et al. Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases. Orphanet J Rare Dis 2022; 17(1): 421. DOI: 10.1186/s13023-022-02577-2

16. Nitschke Y., Baujat G., Botschen U., Wittkampf T., du Moulin M., Stella J. et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticumcanbe caused by mutations in either ENPP1 or ABCC6.Am J Hum Genet 2012; 90(1): 25–39. DOI: 10.1016/j.ajhg.2011.11.020

17. Fãgãrãşan A., Liliana Gozar L., Ghiragosian S-E., Murariu M. , Pop M., Crauciuc A. et al. Severe early-onset manifestations of generalized arterial calcification of infancy (mimicking severe coarctation of the aorta) with ABCC6 gene variant — Case report and literature review. Front Cardiovasc Med 2022; 9: 1032519. DOI: 10.3389/fcvm.2022.1032519

18. Springman A., Forde B., Tolusso L, DeFranco E., Swarr D.T. Twin-twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene-environment interaction? Prenat Diagn 2023; 43(8): 1092–1095. DOI: 10.1002/pd.6396.

19. Ramjan K.A., Roscioli T., Rutsch F., Sillence D., Munns C.F. Generalized arterial calcification of infancy: treatment with bisphosphonates. Nature clinical practice. Nat Clin Pract Endocrinol Metab 2009; 5(3): 167–172. DOI: 10.1038/ncpendmet1067

20. Ferreira C.R., Ziegler S.G., Gupta A., Groden C., Hsu K.S., Gahl W.A. Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification. Am J Med Genet A 2016; 170A(5): 1308–1311. DOI: 10.1002/ajmg.a.37574

21. Akhtar Ali S., NgC., Votava-Smith J.K., RandolphL.M., Pitukcheewanont P. Bisphosphonate therapy in an infant with generalized arterial calcification with an ABCC6 mutation Osteoporos Int 2018; 29(11): 2575–2579. DOI: 10.1007/s00198–018–4639-x

22. Савенкова Н.Д., Аничкова И.В., Левиашвили Ж.Г., Осипова О.С., Карпова Т.В., Имаева Л.Р. и др. Генерализованная артериальная кальцификация у младенцев: клиническое наблюдение. Нефрология 2016; 20(3): 96–107.

23. Khan T., Sinkevicius K.W., Vong S., Avakian A., Leavitt M.C., Malanson H. et al. ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy. Dis Model Mech 2018; 8: 11(10): dmm035691. DOI: 10.1242/dmm.035691

24. Cheng Z., O’Brien K., Howe J., Sullivan C., Schrier D., Lynch A. et al. INZ-701 Prevents Ectopic Tissue Calcification and Restores Bone Architecture and Growth in ENPP1- Deficient Mice. J Bone Miner Res 2021; 36(8): 1594–1604. DOI: 10.1002/jbmr.4315

25. Kawai K., Sato Y., Kawakami R., Sakamoto A., Cornelissen A., Mori M. et al. Generalized Arterial Calcification of Infancy (GACI): Optimizing Care with a Multidisciplinary Approach. J Multidiscip Healthc 2022; 1(15): 1261–1276. DOI: 10.2147/JMDH.S251861