Characterizing the alkaptonuria joint and spine phenotype and assessing the effect of homogentisic acid lowering therapy in a large cohort of 87 patients
- 16 January 2021
- journal article
- research article
- Published by Wiley in Journal of Inherited Metabolic Disease
- Vol. 44 (3), 666-676
- https://doi.org/10.1002/jimd.12363
Abstract
Background A large alkaptonuria (AKU) cohort was studied to better characterise the poorly understood spondyloarthropathy of rare disease AKU. Patients and methods Eighty‐seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. Fifty‐seven attended more than once and received nitisinone 2mg daily. Twenty‐three attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, 18FPETCT, as well as photographs of ochronotic pigment in eyes and ears at baseline when 2mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. Results The prevalence of ochronosis, as well as pain, PETCT & combined pain and PETCT scores, was greatly increased at 90.5, 85.7, 100 and 100% respectively. Joint pain scores were greatest in proximal joints in upper and lower limbs. PETCT joint scores were higher in proximal joints in upper limb but higher in distal joints in the lower limb. Spine pain scores were highest in lumbar, followed by cervical, thoracic and cervical regions at 77.4, 59.5, 46.4 and 25% respectively. PETCT spine scores were highest in thoracic followed by lumbar, cervical and sacroiliac regions at 74.4, 70.7, 64.6 and 47.8% respectively; Ochronosis associated closely with spondyloarthropathy scores (R=0.65; p<0.0001). Nitisinone reversed ochronosis significantly, with a similar pattern of decreased joint and spine disease. Conclusion Spondyloarthropathy is a highly prevalent feature in this NAC cohort. Ochronosis appears to be associated with spondyloarthropathy. Nitisinone decreases ochronosis and had a similar non‐significant effect pattern on spondyloarthropathy.This publication has 35 references indexed in Scilit:
- Knee osteoarthritis in womenCurrent Reviews in Musculoskeletal Medicine, 2013
- Clinical significance of bone changes in osteoarthritisTherapeutic Advances in Musculoskeletal Disease, 2012
- The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuriaArthritis & Rheumatism, 2011
- A 3-year randomized therapeutic trial of nitisinone in alkaptonuriaMolecular Genetics and Metabolism, 2011
- Natural history of alkaptonuria revisited: analyses based on scoring systemsJournal of Inherited Metabolic Disease, 2011
- A quantitative assessment of alkaptonuriaJournal of Inherited Metabolic Disease, 2011
- Natural History of AlkaptonuriaThe New England Journal of Medicine, 2002
- NTBC and AlkaptonuriaAmerican Journal of Human Genetics, 1998
- Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenaseThe Lancet, 1992
- Oxidation of homogentisic acid to ochronotic pigment in connective tissueBiochimica et Biophysica Acta (BBA) - General Subjects, 1969