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Review

Alkaptonuria: Current Perspectives

, &
Pages 37-47 | Published online: 23 Jan 2020

References

  • Garrod AE. Croonian lectures on inborn errors of metabolism, lecture II: alkaptonuria. Lancet. 1908;2:73–79.
  • Fernández-Cañón JM, Granadino B, Beltrán-valero de Bernabé D, et al. The molecular basis of alkaptonuria. Nat Genet. 1996;14(1):19–24. doi:10.1038/ng0996-19
  • La Du BN, Zannoni VG, Laster L, Seegmiller JE. The nature of the defect in tyrosine metabolism in alcaptonuria. J Biol Chem. 1958;230(1):251–260.
  • Zannoni VG, Lomtevas N, Goldfinger S. Oxidation of homogentisic acid to ochronotic pigment in connective tissue. Biochim Biophys Acta. 1969;177(1):94–105. doi:10.1016/0304-4165(69)90068-3
  • Ranganath LR, Jarvis JC, Gallagher JA. Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol. 2013;66(5):367–373. doi:10.1136/jclinpath-2012-200877
  • Ranganath LR, Khedr M, Milan AM, et al. Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre. Mol Genet Metab. 2018;125(1–2):127–134. doi:10.1016/j.ymgme.2018.07.011
  • Ranganath LR, Milan AM, Hughes AT, et al. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment. Ann Rheum Dis. 2016;75(2):362–367. doi:10.1136/annrheumdis-2014-206033
  • Olsson B, Cox TF, Psarelli EE, et al. Relationship between serum concentrations of nitisinone and its effect on homogentisic acid and tyrosine in patients with alkaptonuria. JIMD Rep. 2015;24:21–27.
  • Hughes AT, Milan AM, Davison AS, et al. Serum markers in alkaptonuria: simultaneous analysis of homogentisic acid, tyrosine and nitisinone by liquid chromatography tandem mass spectrometry. Ann Clin Biochem. 2015;52(Pt 5):597–605. doi:10.1177/0004563215571969
  • Hughes AT, Milan AM, Christensen P, et al. Urine homogentisic acid and tyrosine: simultaneous analysis by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;963:106–112. doi:10.1016/j.jchromb.2014.06.002
  • Hughes JH, Wilson PJM, Sutherland H, et al. Dietary restriction of tyrosine and phenylalanine lowers tyrosinaemia associated with nitisinone therapy of alkaptonuria. J Inherit Metab Dis. 2019. doi:10.1002/jimd.12172
  • Cox TF, Psarelli EE, Taylor S, et al. Subclinical Ochronosis Features In Alkaptonuria: a Cross-Sectional Study. BMJ Innovations. 2019. doi:10.1136/bmjinnov-2018-000324
  • Al-Sbou M, Mwafi N. Nine cases of Alkaptonuria in one family in southern Jordan. Rheumatol Int. 2012;32(3):621–625. doi:10.1007/s00296-010-1701-1
  • Janocha S, Wolz W, Srsen S, et al. The human gene for alkaptonuria (AKU) maps to chromosome 3q. Genomics. 1994;19(1):5–8. doi:10.1006/geno.1994.1003
  • Sakthivel S, Zatkova A, Nemethova M, Surovy M, Kadasi L, Saravanan MP. Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence. Ann Hum Genet. 2014;78(3):155–164. doi:10.1111/ahg.12055
  • Srsen S, Varga F. Screening for alkaptonuria in the newborn in Slovakia. Lancet. 1978;2(8089):576. doi:10.1016/S0140-6736(78)92910-0
  • Pollak MR, Chou YH, Cerda JJ, et al. Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2. Nat Genet. 1993;5(2):201–204. doi:10.1038/ng1093-201
  • Fernández-Cañón JM, Peñalva MA. Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. J Biol Chem. 1995;270(36):21199–21205. doi:10.1074/jbc.270.36.21199
  • Granadino B, Beltrán-valero de Bernabé D, Fernández-Cañón JM, Peñalva MA, Rodríguez de Córdoba S. The human homogentisate 1,2-dioxygenase (HGO) gene. Genomics. 1997;43(2):115–122. doi:10.1006/geno.1997.4805
  • Ascher DB, Spiga O, Sekelska M, et al. Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU. Eur J Hum Genet. 2019;27(6):888–902. doi:10.1038/s41431-019-0354-0
  • Zatkova A, Sedlackova T, Radvansky J, et al. Identification of 11 novel homogentisate 1,2 dioxygenase variants in alkaptonuria patients and establishment of a novel LOVD-based HGD mutation database. JIMD Rep. 2012;4:55–65.
  • Spiga O, Cicaloni V, Bernini A, Zatkova A, Santucci A. ApreciseKUre: an approach of precision medicine in a rare disease. BMC Med Inform Decis Mak. 2017;17(1):42. doi:10.1186/s12911-017-0438-0
  • Laschi M, Tinti L, Braconi D, et al. Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria. J Cell Physiol. 2012;227(9):3254–3257. doi:10.1002/jcp.24018
  • Bernardini G, Laschi M, Geminiani M, et al. Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria. J Inherit Metab Dis. 2015;38(5):807–814. doi:10.1007/s10545-015-9829-5
  • Hughes JH, Liu K, Plagge A, et al. Conditional targeting in mice reveals that hepatic homogentisate 1,2-dioxygenase 1 activity is essential in reducing circulating homogentisic acid and for effective therapy 2 in the genetic disease alkaptonuria. Hum Mol Genet. 2019. doi:10.1093/hmg/ddz234
  • Titus GP, Mueller HA, Burgner J, Rodríguez de Córdoba S, Peñalva MA, Timm DE. Crystal structure of human homogentisate dioxygenase. Nat Struct Biol. 2000;7(7):542–546. doi:10.1038/76756
  • Nemethova M, Radvanszky J, Kadasi L, et al. Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on ‘black bone disease’ in Italy. Eur J Hum Genet. 2016;24(1):66–72. doi:10.1038/ejhg.2015.60
  • Zatkova A. An update on molecular genetics of Alkaptonuria (AKU). J Inherit Metab Dis. 2011;34(6):1127–1136. doi:10.1007/s10545-011-9363-z
  • Gupta V, Kalaiarasan P, Faheem M, Singh N, Iqbal MA, Bamezai RN. Dominant negative mutations affect oligomerization of human pyruvate kinase M2 isozyme and promote cellular growth and polyploidy. J Biol Chem. 2010;285(22):16864–16873. doi:10.1074/jbc.M109.065029
  • Bernini A, Galderisi S, Spiga O, et al. Toward a generalized computational workflow for exploiting transient pockets as new targets for small molecule stabilizers: application to the homogentisate 1,2-dioxygenase mutants at the base of rare disease Alkaptonuria. Comput Biol Chem. 2017;70:133–141. doi:10.1016/j.compbiolchem.2017.08.008
  • Rodriguez JM, Timm DE, Titus GP, et al. Structural and functional analysis of mutations in alkaptonuria. Hum Mol Genet. 2000;9(15):2341–2350. doi:10.1093/oxfordjournals.hmg.a018927
  • Langford B, Besford M, Hall A, et al. Alkaptonuria severity score index revisited: analysing the AKUSSI and its subcomponent features. JIMD Rep. 2018;41:53–62.
  • Montagutelli X, Lalouette A, Coude M, Kamoun P, Forest M, Guenet JL. aku, a mutation of the mouse homologous to human alkaptonuria, maps to chromosome 16. Genomics. 1994;19(1):9–11. doi:10.1006/geno.1994.1004
  • Manning K, Fernández-Cañón JM, Montagutelli X, Grompe M. Identification of the mutation in the alkaptonuria mouse model. Mutations in brief no. 216. Online. Hum Mutat. 1999;13(2):171. doi:10.1002/(SICI)1098-1004(1999)13:2<171::AID-HUMU15>3.0.CO;2-W
  • Schmidt SR, Gehrig A, Koehler MR, Schmid M, Muller CR, Kress W. Cloning of the homogentisate 1,2-dioxygenase gene, the key enzyme of alkaptonuria in mouse. Mamm Genome. 1997;8(3):168–171. doi:10.1007/s003359900383
  • Taylor AM, Preston AJ, Paulk NK, et al. Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition. Osteoarthritis Cartilage. 2012;20(8):880–886. doi:10.1016/j.joca.2012.04.013
  • Preston AJ, Keenan CM, Sutherland H, et al. Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone. Ann Rheum Dis. 2014;73(1):284–289. doi:10.1136/annrheumdis-2012-202878
  • Keenan CM, Preston AJ, Sutherland H, et al. Nitisinone arrests but does not reverse ochronosis in Alkaptonuric mice. JIMD Rep. 2015;24:45–50.
  • Ranganath LR, Norman BP, Gallagher JA. Ochronotic pigmentation is caused by homogentisic acid and is the key event in alkaptonuria leading to the destructive consequences of the disease-A review. J Inherit Metab Dis. 2019;42(5):776–792. doi:10.1002/jimd.v42.5
  • Helliwell TR, Gallagher JA, Ranganath L. Alkaptonuria–a review of surgical and autopsy pathology. Histopathology. 2008;53(5):503–512. doi:10.1111/j.1365-2559.2008.03000.x
  • Ranganath LR, Milan AM, Hughes AT, et al. Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria. JIMD. 2019. doi:10.1002/jimd.12181
  • Introne WJ, Phornphutkul C, Bernardini I, McLaughlin K, Fitzpatrick D, Gahl WA. Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation. Mol Genet Metab. 2002;77(1–2):136–142. doi:10.1016/S1096-7192(02)00121-X
  • Taylor AM, Boyde A, Wilson PJ, et al. The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuria. Arthritis Rheum. 2011;63(12):3887–3896. doi:10.1002/art.30606
  • Taylor AM, Wlodarski B, Prior IA, et al. Ultrastructural examination of tissue in a patient with alkaptonuric arthropathy reveals a distinct pattern of binding of ochronotic pigment. Rheumatology (Oxford). 2010;49(7):1412–1414. doi:10.1093/rheumatology/keq027
  • Gallagher JA, Dillon JP, Sireau N, Timmis O, Ranganath LR. Alkaptonuria: an example of a “fundamental disease”–A rare disease with important lessons for more common disorders. Semin Cell Dev Biol. 2016;52:53–57. doi:10.1016/j.semcdb.2016.02.020
  • Taylor AM, Hsueh MF, Ranganath LR, et al. Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing. Rheumatology (Oxford). 2017;56(1):156–164. doi:10.1093/rheumatology/kew355
  • Gallagher JA, Taylor AM, Boyde A, Jarvis JC, Ranganath LR. Recent advances in understanding the pathogenesis of ochronosis. Reumatologia. 2012;50(4):316–323.
  • Millucci L, Braconi D, Bernardini G, et al. Amyloidosis in alkaptonuria. J Inherit Metab Dis. 2015;38(5):797–805. doi:10.1007/s10545-015-9842-8
  • Millucci L, Spreafico A, Tinti L, et al. Alkaptonuria is a novel human secondary amyloidogenic disease. Biochim Biophys Acta. 2012;1822(11):1682–1691. doi:10.1016/j.bbadis.2012.07.011
  • Brunetti G, Tummolo A, D’Amato G, et al. Mechanisms of Enhanced Osteoclastogenesis in Alkaptonuria. Am J Pathol. 2018;188(4):1059–1068. doi:10.1016/j.ajpath.2017.12.008
  • Bernardini G, Leone G, Millucci L, et al. Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria. J Cell Physiol. 2019;234(5):6696–6708. doi:10.1002/jcp.27416
  • Millucci L, Bernardini G, Spreafico A, et al. Histological and ultrastructural characterization of Alkaptonuric tissues. Calcif Tissue Int. 2017;101(1):50–64. doi:10.1007/s00223-017-0260-9
  • Taylor AM, Boyde A, Davidson JS, Jarvis JC, Ranganath LR, Gallagher JA. Identification of trabecular excrescences, novel microanatomical structures, present in bone in osteoarthropathies. Eur Cell Mater. 2012;23:300–308; discussion 308–309. doi:10.22203/eCM.v023a23