TY - JOUR T1 - Subclinical ochronosis features in alkaptonuria: a cross-sectional study JF - BMJ Innovations JO - BMJ Innov SP - 82 LP - 91 DO - 10.1136/bmjinnov-2018-000324 VL - 5 IS - 2-3 AU - Trevor Cox AU - Eftychia Eirini Psarelli AU - Sophie Taylor AU - Hannah Rose Shepherd AU - Mark Robinson AU - Gabor Barton AU - Alpesh Mistry AU - Federica Genovese AU - Daniela Braconi AU - Daniela Giustarini AU - Ranieri Rossi AU - Annalisa Santucci AU - Milad Khedr AU - Andrew Hughes AU - Anna Milan AU - Leah Frances Taylor AU - Elizabeth West AU - Nicolas Sireau AU - Jane Patricia Dillon AU - Nicholas Rhodes AU - James Anthony Gallagher AU - Lakshminarayan Ranganath Y1 - 2019/04/01 UR - http://innovations.bmj.com/content/5/2-3/82.abstract N2 - 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. ER -