A quantitative assessment of alkaptonuria
- 283 Downloads
Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied clinical manifestations mainly by a process of conversion of HGA to a polymeric melanin-like pigment known as ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, successful demonstration of its efficacy in modifying the natural history of AKU requires an effective quantitative assessment tool. We have described two potential tools that could be used to quantitate disease burden in AKU. One tool describes scoring the clinical features that includes clinical assessments, investigations and questionnaires in 15 patients with AKU. The second tool describes a scoring system that only includes items obtained from questionnaires used in 44 people with AKU. Statistical analyses were carried out on the two patient datasets to assess the AKU tools; these included the calculation of Chronbach’s alpha, multidimensional scaling and simple linear regression analysis. The conclusion was that there was good evidence that the tools could be adopted as AKU assessment tools, but perhaps with further refinement before being used in the practical setting of a clinical trial.
KeywordsJoint Replacement Fabry Disease CLIN Group Aortic Valve Disease Cusum Chart
- Committee for Medicinal Products for Human Use (CHMP) (2006) Guidelines on clinical trials in small populations (CHMP/EWP/83561/2005). European Medicines Agency, LondonGoogle Scholar
- Cox TF, Cox MAA (2001) Multidimensional Scaling. Chapman & Hall, Boca RatonGoogle Scholar
- Helliwell TR, Gallagher JA, Ranganath L (2008) Alkaptonuria - a review of surgical and autopsy pathology. Histopathol 53:503–512Google Scholar
- Ranganath LR, Cox TF (2011) Natural history of alkaptonuria revisited: analyses based on scoring systems. JIMD (in press)Google Scholar