RT Journal Article
SR Electronic
T1 Subclinical ochronosis features in alkaptonuria: a cross-sectional study
JF BMJ Innovations
JO BMJ Innov
FD All India Institute of Medical Sciences
SP 82
OP 91
DO 10.1136/bmjinnov-2018-000324
VO 5
IS 2-3
A1 Trevor Cox
A1 Eftychia Eirini Psarelli
A1 Sophie Taylor
A1 Hannah Rose Shepherd
A1 Mark Robinson
A1 Gabor Barton
A1 Alpesh Mistry
A1 Federica Genovese
A1 Daniela Braconi
A1 Daniela Giustarini
A1 Ranieri Rossi
A1 Annalisa Santucci
A1 Milad Khedr
A1 Andrew Hughes
A1 Anna Milan
A1 Leah Frances Taylor
A1 Elizabeth West
A1 Nicolas Sireau
A1 Jane Patricia Dillon
A1 Nicholas Rhodes
A1 James Anthony Gallagher
A1 Lakshminarayan Ranganath
YR 2019
UL http://innovations.bmj.com/content/5/2-3/82.abstract
AB 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.