CHALLENGES OF LOW BONE MINERAL DENSITY IN A FEMALE WITH ALPORT SYNDROME
Alport syndrome
Keywords:
Alport syndrome, kidney, hyperparathyroidism, osteoporosis, denosumab, end stage kidney disease, collagen
Abstract
We report a most unusual case of an adult female with low bone mineral density due to unexpected multiple causes. This is the case of a 47-year-old female with a history of Alport syndrome complicated by end-stage renal disease and premature surgical menopause due to a uterine leiomyoma (which is rarely reported as a component of the syndrome due to collagen damage). The patient received denosumab, with improvement in bone turnover markers and bone mineral density at 1 year of follow-up. Lifelong surveillance is required. Particular aspects of the case are the numerous contributors to osteoporosis and challenges of adequate therapy in such a patient: from premature surgically – induced hypo-estrogenic status, renal hyperparathyroidism, potential impairment of peak bone mass due to the genetic anomaly, and a 7-month course of glucocorticoid medication that she received at the moment the syndrome was misdiagnosed as an inflammatory kidney condition.
References
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[31] M. Almquist, E. Isaksson, N. Clyne, “The treatment of renal hyperparathyroidism,” Endocr Relat Cancer, 27(1):R21-R34, Jan 2020. doi:10.1530/ERC-19-0284.
[32] A. Gopaul, T. Kanagalingam, J. Thain, T. Khan, A. Cowan, N. Sultan, K.K. Clemens, “ Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety,” Arch Osteoporos, 28;16(1):116, Jul 2021. doi:10.1007/s11657-021-00971-0.
[33] P. Zhang, Y. Yu, Y. Gao, G. Yuan, J. Zhang, W. Wang, “Denosumab treatment for refractory hypercalcemia in a hemodialysis patient with tertiary hyperparathyroidism,” Hemodial Int. Jan 2023. doi:10.1111/hdi.13063.
[34] C. Ness, B. Duxbury, L. Van Hove, W. Halseth, E. Tacl E, “Approach to Solitary Thyroid Nodules in Adults”. S D Med, 75(12):569-572, 2022.
[35] N. Dumitru, A, Ghemigian, M. Carsote, SE. Albu, D. Terzea, A. Valea, “Thyroid nodules after initial evaluation by primary health care practitioners: an ultrasound pictorial essay”, Arch Balk Med Union. 51(3):434-8, 2016.
[36] JM. Pappachan, IM. Lahart, AK. Viswanath, F. Borumandi, R. Sodi, MI. Metzendorf, B. Bongaerts, “Parathyroidectomy for adults with primary hyperparathyroidism“, Cochrane Database Syst Rev. 3(3):CD013035, 2023.
[37] L. Radu, M. Carsote, AA. Gheorghisan-Galateanu, SA. Preda, V. Calborean, R. Stanescu, V. Gheorman, DM. Albulescu DM. “Blood Parathyrin and Mineral Metabolism Dynamics. A clinical analyzes“, Rev.Chim. 69(10):2754-8, 2018.
[38] M. Carsote, DN. Paduraru, AE. Nica, A. Valea. “Parathyroidectomy: is vitamin D a player for a good outcome?“, Journal of Medicine and Life. 4(9):348-52, 2016.
[39] K. Sridharan. “Chronic kidney disease mineral and bone disorder: A guide for general practice“. Aust J Gen Pract. 52(1-2):52-57, 2013.
[40] E. Bellorin-Font, E. Rojas, KJ. Martin. Bone Disease in Chronic Kidney Disease and Kidney Transplant. Nutrients, 15(1):167, 2022.
[2] X. Zhang, J. Zhou, S.T. Reeders, K. Tryggvason, “Structure of the human type IV collagen COL4A6 gene, which is mutated in Alport syndrome-associated leiomyomatosis,” Genomics, 1;33(3):473-9, May 1996. doi:10.1006/geno.1996.0222.
[3] Y. Segal, B. Peissel, A. Renieri, M. Marchi, A. Ballabio, Y. Pei, J. Zhou, “LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis,” Am J Hum Genet, 64(1):62-9, Jan 1999. doi:10.1086/302213.
[4] K. Dahan, L. Heidet, J. Zhou, G. Mettler, K.A. Leppig, W. Proesmans, A. David, B. Roussel, J.G. Mongeau, J.M. Gould, J.P. Grunfeld, M.C Gubler, C.Antignac, “Smooth muscle tumors associated with X-linked Alport syndrome: carrier detection in females. Kidney Int. 48(6):1900-6, Dec 1995. doi:10.1038/ki.1995.489.
[5] P. Cochat, P. Guibaud, R. Garcia Torres, B. Roussel, V. Guarner, F. Larbre, “Diffuse leiomyomatosis in Alport syndrome,” J Pediatr, 113(2):339-43, Aug 1988. doi:10.1016/s0022-3476(88)80280-4.
[6] C. Vaicys, C.D. Hunt, R.F. Heary, “Ruptured intracranial aneurysm in an adolescent with Alport's syndrome--a new expression of type IV collagenopathy: case report”, Surg Neurol, 54(1):68-72, Jul 2000. doi:10.1016/s0090-3019(00)00253-6.
[7] S. Bose, S. Pathireddy, K.M. Baradhi, N.R. Aeddula, “Alport's syndrome and intracranial aneurysm: mere coincidence or undiscovered causal relationship,” BMJ Case Rep. 12(1):e228175, Jan 2019. doi:10.1136/bcr-2018-228175.
[8] C.E. Kashtan, Y. Segal, F. Flinter, D. Makanjuola, J.S. Gan, T. Watnick, “Aortic abnormalities in males with Alport syndrome,” Nephrol Dial Transplant. 25(11):3554-60, Nov 2010. doi:10.1093/ndt/gfq271.
[9] T.J. Earl, L. Khan, D. Hagau, A.B. Fernandez, “The spectrum of aortic pathology in Alport syndrome: a case report and review of the literature,” Am J Kidney Dis, 60(5):821-2, Nov 2012. doi:10.1053/j.ajkd.2012.06.024.
[10] M. Rotondi, C. Fallerini, B. Pirali, I. Longo, D. Pasquali, T. Rampino, L. Chiovato, F. Mari, A. Renieri, “A unique patient presenting with concomitant Klinefelter syndrome, Alport syndrome, and craniopharyngioma,” J Androl, 33(6):1155-9, Nov-Dec 2012. doi:10.2164/jandrol.111.016204.
[11] H. Zhang, F.X.H. Wang, “Klinefelter syndrome and Fanconi syndrome in a Chinese boy,” Nephrology (Carlton). Mar 2023. doi:10.1111/nep.14152.
[12] J.A. Savige, P. Branley, P. Neeson, S. Holdsworth, P. Thurlow, “Antithyroid and antiadrenal autoantibodies in antiglomerular basement membrane disease, thin basement membrane disease and Alport syndrome,” Pathology, 30(1):30-3, Feb 1998. doi:10.1080/00313029800169635
[13] D. Noone, C. Licht, “An update on the pathomechanisms and future therapies of Alport syndrome,” Pediatr Nephrol. 28(7):1025-36, Jul 2013. doi:10.1007/s00467-012-2272-z.
[14] J. Savige, H. Storey, E. Watson, J.M Hertz, C. Deltas, A. Renieri, F. Mari, P. Hilbert, P. Plevova, P. Byers, A. Cerkauskaite, M. Gregory, R. Cerkauskiene, D.G. Ljubanovic, F. Becherucci, C. Errichiello, L. Massella, V. Aiello, R. Lennon, L. Hopkinson, A. Koziell, A. Lungu, H.M. Rothe, J. Hoefele, M. Zacchia, T.N. Martic, A. Gupta, A. van Eerde, S. Gear, S. Landini, V. Palazzo, L. Al-Rabadi, K. Claes, A. Corveleyn, E. Van Hoof, M. van Geel, M. Williams, E. Ashton, H. Belge, E. Ars, A. Bierzynska, C. Gangemi, B.S. Lipska-Ziętkiewicz, “Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria,” Eur J Hum Genet, 29(8):1186-1197, Aug 2021. doi:10.1038/s41431-021-00858-1.
[15] L.M. Bersie-Larson, L. Gyoneva, D.J. Goodman, K.D. Dorfman, Y. Segal, V.H. Barocas, “Glomerular filtration and podocyte tensional homeostasis: importance of the minor type IV collagen network,” Biomech Model Mechanobiol. 19(6):2433-2442, Dec 2020. doi:10.1007/s10237-020-01347-y.
[16] J. Kruegel, D. Rubel, O. Gross, “Alport syndrome--insights from basic and clinical research,” Nat Rev Nephrol, 9(3):170-8, Mar 2013. doi:10.1038/nrneph.2012.259.
[17] M. Levy, J. Feingold, “Estimating prevalence in single-gene kidney diseases progressing to renal failure,” Kidney Int. 58(3):925-43, Sep 2000. doi:10.1046/j.1523-1755.2000.00250.x.
[18] B.G. Hudson, K. Tryggvason, M. Sundaramoorthy, E.G. Neilson, “Alport's syndrome, Goodpasture's syndrome, and type IV collagen”, N Engl J Med. 348(25):2543-56, Jun 2003. doi:10.1056/NEJMra022296.
[19] J. Savige, F. Ariani, F. Mari, M. Bruttini, A. Renieri, O. Gross, C. Deltas, F. Flinter, J. Ding, D.P. Gale, M. Nagel, M. Yau, L. Shagam, R. Torra, E. Ars, J. Hoefele, G. Garosi, H. Storey, “Expert consensus guidelines for the genetic diagnosis of Alport syndrome,” Pediatr Nephrol. 34(7):1175-1189, Jul 2019. doi:10.1007/s00467-018-3985-4.
[20] M.N. Rheault, J. Savige, M.J. Randles, A. Weinstock, M. Stepney, A.N. Turner, G. Parziale, O. Gross, F.A. Flinter, J.H. Miner, S. Lagas, S. Gear, R. Lennon, “The importance of clinician, patient and researcher collaborations in Alport syndrome,” Pediatr Nephrol, 35(5):733-742, May 2020. doi:10.1007/s00467-019-04241-7.
[21] J. Savige, M. Gregory, O. Gross, C. Kashtan, J. Ding, F. Flinter, “Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy,” J Am Soc Nephrol. 24(3):364-75, Feb 2013. doi:10.1681/ASN.2012020148.
[22] E. Daina, P. Cravedi, M. Alpa, D. Roccatello, S. Gamba, A. Perna, F. Gaspari, G. Remuzzi, P. Ruggenenti, “A multidrug, antiproteinuric approach to alport syndrome: a ten-year cohort study,” Nephron, 130(1):13-20, 2015. doi: 10.1159/000381480. Epub 2015 Apr 21.
[23] R. Torra, M. Furlano, “New therapeutic options for Alport syndrome,” Nephrol Dial Transplant, 1;34(8):1272-1279, Aug 2019. doi:10.1093/ndt/gfz131.
[24] C.E. Kashtan, “Alport Syndrome: Achieving Early Diagnosis and Treatment,” Am J Kidney Dis, 77(2):272-279, Feb 2021. doi: 10.1053/j.ajkd.2020.03.026.
[25] E. Chavez, J. Rodriguez, Y. Drexler, A. Fornoni, “Novel Therapies for Alport Syndrome”, Front Med (Lausanne), 25;9:848389, Apr 2022. doi:10.3389/fmed.2022.848389.
[26] K. Wesseling-Perry, I.B. Salusky, “Chronic kidney disease: mineral and bone disorder in children,” Semin Nephrol, 33(2):169-79, Mar 2013. doi:10.1016/j.semnephrol.2012.12.017.
[27] F. Mac Way, M. Lessard, M.H. Lafage-Proust, “Pathophysiology of chronic kidney disease-mineral and bone disorder”, Joint Bone Spine, 79(6):544-9, Dec 2012. doi:10.1016/j.jbspin.2012.09.014.
[28] C.Y. Hsu, L.R. Chen, K.H. Chen, “Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review,” Int J Mol Sci, 18;21(18):6846, Sep 2020. doi:10.3390/ijms21186846.
[29] M.L. Melamed, M. Chonchol, O.M. Gutiérrez, K. Kalantar-Zadeh, J. Kendrick, K. Norris, J.J. Scialla, R. Thadhani, “The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation,” Am J Kidney Dis, 72(6):834-845, Dec 2018. doi:10.1053/j.ajkd.2018.06.031.
[30] L. Zand, R. Kumar, “The Use of Vitamin D Metabolites and Analogues in the Treatment of Chronic Kidney Disease,” Endocrinol Metab Clin North Am, 46(4):983-1007, Dec 2017. doi:10.1016/j.ecl.2017.07.008.
[31] M. Almquist, E. Isaksson, N. Clyne, “The treatment of renal hyperparathyroidism,” Endocr Relat Cancer, 27(1):R21-R34, Jan 2020. doi:10.1530/ERC-19-0284.
[32] A. Gopaul, T. Kanagalingam, J. Thain, T. Khan, A. Cowan, N. Sultan, K.K. Clemens, “ Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety,” Arch Osteoporos, 28;16(1):116, Jul 2021. doi:10.1007/s11657-021-00971-0.
[33] P. Zhang, Y. Yu, Y. Gao, G. Yuan, J. Zhang, W. Wang, “Denosumab treatment for refractory hypercalcemia in a hemodialysis patient with tertiary hyperparathyroidism,” Hemodial Int. Jan 2023. doi:10.1111/hdi.13063.
[34] C. Ness, B. Duxbury, L. Van Hove, W. Halseth, E. Tacl E, “Approach to Solitary Thyroid Nodules in Adults”. S D Med, 75(12):569-572, 2022.
[35] N. Dumitru, A, Ghemigian, M. Carsote, SE. Albu, D. Terzea, A. Valea, “Thyroid nodules after initial evaluation by primary health care practitioners: an ultrasound pictorial essay”, Arch Balk Med Union. 51(3):434-8, 2016.
[36] JM. Pappachan, IM. Lahart, AK. Viswanath, F. Borumandi, R. Sodi, MI. Metzendorf, B. Bongaerts, “Parathyroidectomy for adults with primary hyperparathyroidism“, Cochrane Database Syst Rev. 3(3):CD013035, 2023.
[37] L. Radu, M. Carsote, AA. Gheorghisan-Galateanu, SA. Preda, V. Calborean, R. Stanescu, V. Gheorman, DM. Albulescu DM. “Blood Parathyrin and Mineral Metabolism Dynamics. A clinical analyzes“, Rev.Chim. 69(10):2754-8, 2018.
[38] M. Carsote, DN. Paduraru, AE. Nica, A. Valea. “Parathyroidectomy: is vitamin D a player for a good outcome?“, Journal of Medicine and Life. 4(9):348-52, 2016.
[39] K. Sridharan. “Chronic kidney disease mineral and bone disorder: A guide for general practice“. Aust J Gen Pract. 52(1-2):52-57, 2013.
[40] E. Bellorin-Font, E. Rojas, KJ. Martin. Bone Disease in Chronic Kidney Disease and Kidney Transplant. Nutrients, 15(1):167, 2022.
Published
2023-04-14
How to Cite
Voinea, I.-A., Trandafir, A.-I., Gheorghe, A.-M., Carsote, M., Nistor, C., Petrova, E., & Ghemigian, A. (2023). CHALLENGES OF LOW BONE MINERAL DENSITY IN A FEMALE WITH ALPORT SYNDROME. Romanian Journal of Clinical Research, 6(1). https://doi.org/10.33695/rjcr.v6i1.179
Section
Articles
