@article {Cox82, author = {Trevor Cox and Eftychia Eirini Psarelli and Sophie Taylor and Hannah Rose Shepherd and Mark Robinson and Gabor Barton and Alpesh Mistry and Federica Genovese and Daniela Braconi and Daniela Giustarini and Ranieri Rossi and Annalisa Santucci and Milad Khedr and Andrew Hughes and Anna Milan and Leah Frances Taylor and Elizabeth West and Nicolas Sireau and Jane Patricia Dillon and Nicholas Rhodes and James Anthony Gallagher and Lakshminarayan Ranganath}, title = {Subclinical ochronosis features in alkaptonuria: a cross-sectional study}, volume = {5}, number = {2-3}, pages = {82--91}, year = {2019}, doi = {10.1136/bmjinnov-2018-000324}, publisher = {BMJ Specialist Journals}, abstract = {Background Alkaptonuria (AKU) is present from birth, yet clinical effects are considered to appear later in life. Morbidity of AKU, considered irreversible, is secondary to ochronosis. Age of ochronosis onset is not clearly known. Nitisinone profoundly lowers homogentisic acid (HGA), the metabolic defect in AKU. Nitisinone also arrests ochronosis and slows progression of AKU. However, tyrosinaemia post-nitisinone has been associated with corneal keratopathy, rash and cognitive impairment in HT 1. The optimal time to start nitisinone in AKU is unknown.Methods In an open, cross-sectional, single-site study, 32 patients with AKU were to be recruited. The primary outcome was presence of ochronosis in an ear biopsy. Secondary outcomes included analysis of photographs of eyes/ears, serum/urine HGA, markers of tissue damage/inflammation/oxidation, MRI imaging, gait, quality of life and Alkaptonuria Severity Score Index (qAKUSSI).Results Thirty patients, with mean age (SD) 38 (14) years, were recruited. Percentage pigmentation within ear biopsies increased with age. Ear pigmentation was detected in a 20-year-old woman implying ochronosis can start in patients before the age of 20. Gait and qAKUSSI were outside the normal range in all the patients with AKU.Conclusions Ochronosis can be present before age 20 years.}, issn = {2055-8074}, URL = {https://innovations.bmj.com/content/5/2-3/82}, eprint = {https://innovations.bmj.com/content/5/2-3/82.full.pdf}, journal = {BMJ Innovations} }