Research & Literature

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

Nemethova M, Radvanszky J, Kadasi L, et al.

European journal of human genetics : EJHG 2016; (24(1)):66-72 doi:10.1038/ejhg.2015.60.

Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.

Keenan CM, Preston AJ, Sutherland H, et al.

JIMD reports 2015; (24()):45-50 doi:10.1007/8904_2015_437.

Cervical Spondylotic Myelopathy due to the Ochronotic Arthropathy of the Cervical Spine.

Li N, Tian W, Yuan Q, He D

Journal of Korean Neurosurgical Society 2016; (59(1)):65-8 doi:10.3340/jkns.2016.59.1.65.

Quick Diagnosis of Alkaptonuria by Homogentisic Acid Determination in Urine Paper Spots.

Jacomelli G, Micheli V, Bernardini G, et al.

JIMD reports 2017; (31()):51-56 doi:10.1007/8904_2016_554.

Ochronosis as Etiology of Requiring Total Knee Arthroplasty-A Case Series.

Pierce TP, Issa K, Ramirez A, et al.

Surgical technology international 2016; (29()):261-264.

The effect of nitisinone on homogentisic acid and tyrosine: a two-year survey of patients attending the National Alkaptonuria Centre, Liverpool.

Milan AM, Hughes AT, Davison AS, et al.

Annals of clinical biochemistry 2017; (54(3)):323-330 doi:10.1177/0004563217691065.

Histological and Ultrastructural Characterization of Alkaptonuric Tissues.

Millucci L, Bernardini G, Spreafico A, et al.

Calcified tissue international 2017; (101(1)):50-64 doi:10.1007/s00223-017-0260-9.

Severe Aortic Valve Stenosis Due to Alkaptonuric Ochronosis.

El-Sayed Ahmed MM, Hussain O, Ott DA, Aftab M

Seminars in cardiothoracic and vascular anesthesia 2017; (21(4)):364-366 doi:10.1177/1089253217720284.

Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria.

Khedr M, Judd S, Briggs MC, et al.

JIMD reports 2018; (40()):31-37 doi:10.1007/8904_2017_62.

"As Black as Ink": A Case of Alkaptonuria-Associated Myelopathy and a Review of the Literature.

Donaldson CJ, Mitchell SL, Riley LH, Kebaish KM

Spine 2019; (44(1)):E53-E59 doi:10.1097/BRS.0000000000002755.

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Griffin R, Psarelli EE, Cox TF, et al.

Data in brief 2018; (20()):1620-1628 doi:10.1016/j.dib.2018.09.021.

Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU.

Ascher DB, Spiga O, Sekelska M, et al.

European journal of human genetics : EJHG 2019; (27(6)):888-902 doi:10.1038/s41431-019-0354-0.

Exogenous ochronosis: the failure of depigmenting creams.

Sánchez-Martínez EM, García-Briz MI, Moneva-Léniz LM, et al.

Dermatology online journal 2019; (25(4)).

Management of a pseudarthrosis with sagittal malalignment in a patient with ochronotic spondyloarthropathy.

Alkasem W, Boissiere L, Obeid I, Bourghli A

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 2019; (28(10)):2283-2289 doi:10.1007/s00586-019-06020-2.

Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisinone therapy of alkaptonuria.

Hughes JH, Wilson PJM, Sutherland H, et al.

Journal of inherited metabolic disease 2020; (43(2)):259-268 doi:10.1002/jimd.12172.

Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.

Ranganath LR, Milan AM, Hughes AT, et al.

Journal of inherited metabolic disease 2020; (43(4)):737-747 doi:10.1002/jimd.12181.

Presentation of 14 alkaptonuria patients from Turkey.

Akbaba AI, Ozgül RK, Dursun A

Journal of pediatric endocrinology & metabolism : JPEM 2020; (33(2)):289-294.

Clinical and radiological outcomes of total joint arthroplasty in patients with ochronotic arthropathy.

Rajkumar N, Soundarrajan D, Dhanasekararaja P, Rajasekaran S

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 2020; (30(5)):923-929 doi:10.1007/s00590-020-02651-0.

Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India.

Danda S, Mohan S, Devaraj P, et al.

Clinical rheumatology 2020; (39(9)):2743-2749 doi:10.1007/s10067-020-05020-8.

The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma.

Judd S, Khedr M, Milan AM, et al.

JIMD reports 2020; (53(1)):45-60 doi:10.1002/jmd2.12084.

A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care.

Rudebeck M, Scott C, Sireau N, Ranganath L

JIMD reports 2020; (53(1)):71-79 doi:10.1002/jmd2.12101.

Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial.

Ranganath LR, Psarelli EE, Arnoux JB, et al.

The lancet. Diabetes & endocrinology 2020; (8(9)):762-772 doi:10.1016/S2213-8587(20)30228-X.

Long-Term Outcomes of the Knee and Hip Arthroplasties in Patients with Alkaptonuria.

Al-Ajlouni JM, Alisi MS, Yasin MS, et al.

Arthroplasty today 2020; (6(4)):689-693 doi:10.1016/j.artd.2020.07.037.

Cervical Myelopathy Due to Ochronosis: An Intraoperative Suspicion.

Alisi MS, Al-Saber MG, Abdulelah AA, et al.

The American journal of case reports 2020; (21()):e924575 doi:10.12659/AJCR.924575.

Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces.

Hughes JH, Keenan CM, Sutherland H, et al.

Calcified tissue international 2021; (108(2)):207-218 doi:10.1007/s00223-020-00764-6.

Exogenous Ochronosis (EO): Skin lightening cream causing rare caviar-like lesion with banana-like pigments; review of literature and histological comparison with endogenous counterpart.

Qorbani A, Mubasher A, Sarantopoulos GP, et al.

Autopsy & case reports 2020; (10(4)):e2020197 doi:10.4322/acr.2020.197.

Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

Yuce Inel T, Kisa PT, Balci A, et al.

Modern rheumatology 2021; (31(5)):1031-1037 doi:10.1080/14397595.2020.1868121.

A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature.

Chu P, Cuellar MC, Bracken SJ, Tarrant TK

Current allergy and asthma reports 2021; (21(3)):19 doi:10.1007/s11882-021-01002-1.

Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients.

Kisa PT, Gunduz M, Dorum S, et al.

European journal of medical genetics 2021; (64(5)):104197 doi:10.1016/j.ejmg.2021.104197.

Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: Analysis of a large cohort of eighty-one alkaptonuria patients.

Ranganath LR, Heseltine T, Khedr M, Fisher MF

Molecular genetics and metabolism 2021; (133(3)):324-331 doi:10.1016/j.ymgme.2021.05.007.

Exogenous ochronosis associated with hydroquinone: a systematic review.

Ishack S, Lipner SR

International journal of dermatology 2022; (61(6)):675-684 doi:10.1111/ijd.15878.

Alkaptonuria in Russia.

Soltysova A, Kuzin A, Samarkina E, Zatkova A

European journal of human genetics : EJHG 2022; (30(2)):237-242 doi:10.1038/s41431-021-00955-1.

Efficacy of Phenylalanine- and Tyrosine-Restricted Diet in Alkaptonuria Patients on Nitisinone Treatment: Case Series and Review of Literature.

Teke Kisa P, Eroglu Erkmen S, Bahceci H, et al.

Annals of nutrition & metabolism 2022; (78(1)):48-60 doi:10.1159/000519813.

A molecular spectroscopy approach for the investigation of early phase ochronotic pigment development in Alkaptonuria.

Bernini A, Petricci E, Atrei A, et al.

Scientific reports 2021; (11(1)):22562 doi:10.1038/s41598-021-01670-z.

Alkaptonuria: clinical manifestations and an updated approach to treatment of a rare disease.

Roopnarinesingh RC, Donlon NE, Reynolds JV

BMJ case reports 2021; (14(12)) doi:10.1136/bcr-2021-244240.

Effects of a protein-restricted diet on body weight and serum tyrosine concentrations in patients with alkaptonuria.

Olsson B, Ranganath L, Arnoux JB, et al.

JIMD reports 2022; (63(1)):41-49 doi:10.1002/jmd2.12255.

Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria-An approach using statistical modelling.

Ranganath LR, Milan AM, Hughes AT, et al.

JIMD reports 2022; (63(1)):80-92 doi:10.1002/jmd2.12261.

Characterization of changes in the tyrosine pathway by 24-h profiling during nitisinone treatment in alkaptonuria.

Ranganath LR, Milan AM, Hughes AT, et al.

Molecular genetics and metabolism reports 2022; (30()):100846 doi:10.1016/j.ymgmr.2022.100846.

Association of alkaptonuria and low dose nitisinone therapy with cataract formation in a large cohort of patients.

Ahmad MSZ, Ahmed M, Khedr M, et al.

JIMD reports 2022; (63(4)):351-360 doi:10.1002/jmd2.12288.

Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment.

Ranganath LR, Milan AM, Hughes AT, et al.

Metabolites 2022; (12(8)) doi:10.3390/metabo12080772.

Revisiting Quantification of Phenylalanine/Tyrosine Flux in the Ochronotic Pathway during Long-Term Nitisinone Treatment of Alkaptonuria.

Ranganath LR, Hughes AT, Davison AS, et al.

Metabolites 2022; (12(10)) doi:10.3390/metabo12100920.

Analysis of the Phenotype Differences in Siblings with Alkaptonuria.

Zatkova A, Olsson B, Ranganath LR, Imrich R

Metabolites 2022; (12(10)) doi:10.3390/metabo12100990.

Nutritional interventions for patients with alkaptonuria: A minireview.

Imrich R, Zatkova A, Lukacova O, et al.

Endocrine regulations 2023; (57(1)):61-67 doi:10.2478/enr-2023-0008.

Exogenous Ochronosis With Ocular Involvement From Chronic Use of Teavigo.

Vempuluru VS, Laiton A, Milman T, et al.

Ophthalmic plastic and reconstructive surgery 2023; (39(5)):e139-e142 doi:10.1097/IOP.0000000000002395.

Alkaptonuria.

Bernardini G, Braconi D, Zatkova A, et al.

Nature reviews. Disease primers 2024; (10(1)):16 doi:10.1038/s41572-024-00498-x.

Avulsive Achilles Tendon Rupture in a Patient With Alkaptonuria: A Case Report.

Fabião L, França G, Cunha A, et al.

Cureus 2024; (16(6)):e62631 doi:10.7759/cureus.62631.

Anthropometric, Body Composition, and Nutritional Indicators with and without Nutritional Intervention during Nitisinone Therapy in Alkaptonuria.

Ranganath LR, Khedr M, Milan AM, et al.

Nutrients 2024; (16(16)) doi:10.3390/nu16162722.

A rare differential diagnosis of aortic stenosis with a black aortic valve: A case report.

Rangwala ZS, Radhakrishnan BK, Patel PS, et al.

The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology 2024; (76(1)):128 doi:10.1186/s43044-024-00553-8.

Direct repair of the chronic ochronotic Achilles tendon rupture: a case report.

Yokoe T, Nagasawa M, Tajima T, et al.

BMC musculoskeletal disorders 2024; (25(1)):843 doi:10.1186/s12891-024-07973-2.

Alkaptonuria: Clinical Spectrum of a Diagnosed Case in Bahrain With a Literature Review.

Alsahlawi Z, Salman LI, Alaradi AM, et al.

Cureus 2025; (17(1)):e77174 doi:10.7759/cureus.77174.

Clinical and dermoscopic characteristics of exogenous ochronosis: results of a multicentre study by the International Dermoscopy Society Dermoscopy in Skin of Color Task Force.

Vinay K, Mehta H, Bhat YJ, et al.

Clinical and experimental dermatology 2025; (50(9)):1777-1785 doi:10.1093/ced/llaf159.

Exogenous ochronosis by hydroquinone is not caused by inhibition of homogentisate dioxygenase but potentially by tyrosinase-catalysed metabolism of hydroquinone.

Ito S, Kolbe L, Weets G, et al.

The British journal of dermatology 2025; (193(5)):959-967 doi:10.1093/bjd/ljaf273.

Musculoskeletal Manifestations of Alkaptonuria: A Case-Based Review of Literature.

K A, Kumar S, M V B, et al.

Cureus 2025; (17(8)):e90841 doi:10.7759/cureus.90841.

Ochronotic Deposition in Alkaptonuria: Semiquinone-Mediated Oxidative Coupling and Metabolic Drivers of Homogentisic Acid Accumulation.

Grasso D, Balloni V, Baratto MC, et al.

International journal of molecular sciences 2025; (26(19)) doi:10.3390/ijms26199674.

A Rare Diagnosis in a Resource-Limited Setting: Alkaptonuria in a Young Dominican Child.

Ortiz Hernández IY, García Grullon C, Rijo Florimon K, et al.

Cureus 2025; (17(9)):e92939 doi:10.7759/cureus.92939.

Mechanistic Insights into Tyrosinase-Catalyzed Metabolism of Hydroquinone: Implications for the Etiology of Exogenous Ochronosis and Cytotoxicity to Melanocytes.

Ito S, Kolbe L, Rogers T, et al.

International journal of molecular sciences 2025; (26(21)) doi:10.3390/ijms262110734.

Clinical and molecular characteristics of Chinese patients with alkaptonuria: 4-year follow-up of a pediatric patient and literature review.

Qiu X, Liu Y, Shao Y, et al.

Molecular genetics and metabolism reports 2025; (45()):101276 doi:10.1016/j.ymgmr.2025.101276.

Total knee arthroplasty in ochronosis: a case of intraoperative patellar tendon rupture and review of literature.

Acharya KKV, Mann IS, Kumar S

Irish journal of medical science 2026; (195(2)):787-792 doi:10.1007/s11845-025-04268-w.

Effect of Nitisinone on Aortic Stenosis Disease Progression in Patients With Alkaptonuria: An Analysis of the Suitability of Nitisinone in Alkaptonuria (SONIA) 2 Study.

Bruce C, Meenamkuzhy-Hariharan P, Hussain S, et al.

Cureus 2025; (17(12)):e100123 doi:10.7759/cureus.100123.

Clinical and Dermoscopic Characteristics of Facial Hyperpigmentation Disorders in Skin of Color.

Mansilla-Polo M, Díaz-Gómez CJ, Morgado-Carrasco D

Actas dermo-sifiliograficas 2026; (117(7)):104637 doi:10.1016/j.ad.2026.104637.

Spontaneous Achilles tendon rupture as the initial presentation of ochronosis: a case report.

Al-Zagebah A, Elazab M, Muhtaseb R, et al.

International journal of surgery case reports 2026; (138(5)):1967-1970 doi:10.1097/RC9.0000000000000462.

Clinically probable alkaptonuria-associated ochronosis presenting as multilevel cervical disc herniation with myeloradiculopathy managed by three-level C4-7 anterior cervical discectomy and fusion: a case report.

Wu Z, Sun B, Sheng J, et al.

Frontiers in endocrinology 2026; (17()):1805510 doi:10.3389/fendo.2026.1805510.

[Exogenous ochronosis: An underdiagnosed cause of acquired facial hyperpigmentation].

Pelloux M, Lesport C, Guinet É, Gil H

Annales de pathologie 2026; doi:10.1016/j.annpat.2026.08.001.