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Etiology, Epidemiology, Pathophysiology, Diagnosis, Differential Diagnosis, Treatment, Prognosis and Complications of Alkaptomuria

Muralinath E., Guruprasad M., Madhavi Latha C., Sheethal U., Rajitha V., Manohar U., Srinadh G., Rohitha K.

Abstract


Alkaptonuria is a metabolic disorder that leads to harmful abnormal deposits in different tissues throughout the body because of disrupted tyrosine metabolism. This article explicits the disorder's etiology, epidemiology, pathophysiology, and clinical presentations, especially its ocular manifestations. It also addresses the role of the interprofessional team regarding evaluation and treatment of patiens along with this condition.


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Fernández-Cañón, J. M., Granadino, B., Beltrán-Valero de Bernabé, D., Renedo, M., Fernández-Ruiz, E., Peñalva, M. A., & Rodríguez de Córdoba, S. (1996). The molecular basis of alkaptonuria. Nature Genetics, 14(1), 19–24. https://doi.org/10.1038/ng0996-19

Mistry, J. B., Bukhari, M., & Taylor, A. M. (2013). Alkaptonuria. Rare Diseases, 1, e27475. https://doi.org/10.4161/rdis.27475

Lindner, M., & Bertelmann, T. (2014). On the ocular findings in ochronosis: A systematic review of literature. BMC Ophthalmology, 14, Article 12. https://doi.org/10.1186/1471-2415-14-12

Stenn, F. F., Milgram, J. W., Lee, S. L., Weigand, R. J., & Veis, A. (1977). Biochemical identification of homogentisic acid pigment in an ochronotic Egyptian mummy. Science, 197(4303), 566–568. https://doi.org/10.1126/science.327543

Garrod, A. E. (1996). The incidence of alkaptonuria: A study in chemical individuality (Original work published 1902). Molecular Medicine, 2(3), 274–282.

Scriver, C. R. (2008). Garrod’s Croonian Lectures (1908) and the charter “Inborn Errors of Metabolism”: Albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. Journal of Inherited Metabolic Disease, 31(5), 580–598. https://doi.org/10.1007/s10545-008-0962-6

La Du, B. N., Zannoni, V. G., Laster, L., & Seegmiller, J. E. (1958). The nature of the defect in tyrosine metabolism in alkaptonuria. Journal of Biological Chemistry, 230(1), 251–260.

Janocha, S., Wolz, W., Srsen, S., Srsnova, K., Montagutelli, X., Guénet, J. L., Grimm, T., Kress, W., & Müller, C. R. (1994). The human gene for alkaptonuria (AKU) maps to chromosome 3q. Genomics, 19(1), 5–8. https://doi.org/10.1006/geno.1994.1002

Zatková, A. (2011). An update on molecular genetics of alkaptonuria (AKU). Journal of Inherited Metabolic Disease, 34(6), 1127–1136. https://doi.org/10.1007/s10545-011-9375-1

Jónsson, H., Sulem, P., Kehr, B., Kristmundsdottir, S., Zink, F., Hjartarson, E., … Stefansson, K. (2017). Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature, 549(7673), 519–522. https://doi.org/10.1038/nature24018

Goicoechea de Jorge, E., Lorda, I., Gallardo, M. E., Pérez, B., Pérez de Ferrán, C., Mendoza, H., & Rodríguez de Córdoba, S. (2002). Alkaptonuria in the Dominican Republic: Identification of the founder AKU mutation and further evidence of mutation hot spots in the HGO gene. Journal of Medical Genetics, 39(7), e40. https://doi.org/10.1136/jmg.39.7.e40

Khalil, R., Ali, D., Mwafi, N., Alsaraireh, A., Obeidat, L., Albsoul, E., & Al Sbou’, I. (2021). Variant analysis of alkaptonuria families with significant founder effect in Jordan. BioMed Research International, 2021, Article 1515641. https://doi.org/10.1155/2021/1515641

Phornphutkul, C., Introne, W. J., Perry, M. B., Bernardini, I., Murphey, M. D., Fitzpatrick, D. L., … Gahl, W. A. (2002). Natural history of alkaptonuria. New England Journal of Medicine, 347(26), 2111–2121. https://doi.org/10.1056/NEJMoa021736

Jiang, L., Cao, L., Fang, J., Yu, X., Dai, X., & Miao, X. (2019). Ochronotic arthritis and ochronotic Achilles tendon rupture in alkaptonuria: A 6-year follow-up case report in China. Medicine, 98(34), e16837. https://doi.org/10.1097/MD.0000000000016837

Gaines, J. J. (1989). The pathology of alkaptonuric ochronosis. Human Pathology, 20(1), 40–46. https://doi.org/10.1016/0046-8177(89)90064-8

Borman, P., Bodur, H., & Ciliz, D. (2002). Ochronotic arthropathy. Rheumatology International, 21(5), 205–209. https://doi.org/10.1007/s00296-001-0177-2

Kisa, P. T., Gunduz, M., Dorum, S., Uzun, O. U., Cakar, N. E., Yildirim, G. K., … Arslan, N. (2021). Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients. European Journal of Medical Genetics, 64(5), 104197. https://doi.org/10.1016/j.ejmg.2021.104197

Kampik, A., Sani, J. N., & Green, W. R. (1980). Ocular ochronosis: Clinicopathological, histochemical, and ultrastructural studies. Archives of Ophthalmology, 98(8), 1441–1447. https://doi.org/10.1001/archopht.1980.01020040373008

Chévez-Barrios, P., & Font, R. L. (2004). Pigmented conjunctival lesions as initial manifestation of ochronosis. Archives of Ophthalmology, 122(7), 1060–1063. https://doi.org/10.1001/archopht.122.7.1060

Kumar, A., Karthikeyan, K., & Vyas, M. T. (2015). Osler’s sign revisited. Indian Dermatology Online Journal, 6(4), 308–309. https://doi.org/10.4103/2229-5178.156397

Ben Rayana, N., Chahed, N., Khochtali, S., Ghorbel, M., Hamdi, R., Rouis, M., Bouajina, I., & Hamida, F. B. (2008). Ocular ochronosis: A case report. Journal Français d’Ophtalmologie, 31(6 Pt 1), 624.

Bacchetti, S., Zeppieri, M., & Brusini, P. (2004). A case of ocular ochronosis and chronic open-angle glaucoma: Merely coincidental? Acta Ophthalmologica Scandinavica, 82(5), 631–632. https://doi.org/10.1111/j.1600-0420.2004.00327.x

Ehongo, A., Schrooyen, M., & Pereleux, A. (2005). Important bilateral corneal astigmatism in a case of ocular ochronosis. Bulletin de la Société Belge d’Ophtalmologie, (295), 17–21.

John, S. S., Padhan, P., Mathews, J. V., & David, S. (2009). Acute anterior uveitis as the initial presentation of alkaptonuria. Journal of Postgraduate Medicine, 55(1), 35–37. https://doi.org/10.4103/0022-3859.48435

Ashton, N., Kirker, J. G., & Lavery, F. S. (1964). Ocular findings in a case of hereditary ochronosis. British Journal of Ophthalmology, 48(8), 405–415. https://doi.org/10.1136/bjo.48.8.405

Damarla, N., Linga, P., Goyal, M., Tadisina, S. R., Reddy, G. S., & Bommisetti, H. (2017). Alkaptonuria: A case report. Indian Journal of Ophthalmology, 65(6), 518–521. https://doi.org/10.4103/ijo.IJO_613_16

Pandey, R., Kumar, A., Garg, R., Khanna, P., & Darlong, V. (2011). Perioperative management of patient with alkaptonuria and associated multiple comorbidities. Journal of Anaesthesiology Clinical Pharmacology, 27(2), 259–261. https://doi.org/10.4103/0970-9185.81844

Anikster, Y., Nyhan, W. L., & Gahl, W. A. (1998). NTBC and alkaptonuria. American Journal of Human Genetics, 63(3), 920–921.

Introne, W. J., Perry, M. B., Troendle, J., Tsilou, E., Kayser, M. A., Suwannarat, P., … Gahl, W. A. (2011). A 3-year randomized therapeutic trial of nitisinone in alkaptonuria. Molecular Genetics and Metabolism, 103(4), 307–314. https://doi.org/10.1016/j.ymgme.2011.04.016

Suwannarat, P., O’Brien, K., Perry, M. B., Sebring, N., Bernardini, I., Kaiser-Kupfer, M. I., … Gahl, W. A. (2005). Use of nitisinone in patients with alkaptonuria. Metabolism, 54(6), 719–728. https://doi.org/10.1016/j.metabol.2005.01.035

de Haas, V., Carbasius Weber, E. C., de Klerk, J. B., Bakker, H. D., Smit, G. P., Huijbers, W. A., Duran, M., & Poll-The, B. T. (1998). The success of dietary protein restriction in alkaptonuria patients is age-dependent. Journal of Inherited Metabolic Disease, 21(8), 791–798.

Morava, E., Kosztolányi, G., Engelke, U. F., & Wevers, R. A. (2003). Reversal of clinical symptoms and radiographic abnormalities with protein restriction and ascorbic acid in alkaptonuria. Annals of Clinical Biochemistry, 40(1), 108–111. https://doi.org/10.1258/000456303321153874


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