Alkaptonuria Severity Score Index Revisited: Analysing the AKUSSI and Its Subcomponent Features

  • Bryony LangfordEmail author
  • Megan Besford
  • Aimée Hall
  • Lucy Eddowes
  • Oliver Timmis
  • James A. Gallagher
  • Lakshminarayan Ranganath
Research Report
Part of the JIMD Reports book series (JIMD, volume 41)


Background: Alkaptonuria (AKU) is a rare disorder with no licensed treatment; nitisinone may reduce symptoms and progression. The All Alkaptonuria Severity Score Index (AKUSSI) measures disease severity in clinical, joint and spine domains, with 57 subcomponent feature scores. Our primary aim was to assess tools for validating scores such as the AKUSSI by detecting relationships between features both before and during nitisinone treatment.

Methods: AKUSSI measurements from nitisinone-treated patients visiting the National AKU Centre between 01-Jun-2012 and 31-May-2016 were analysed pre-treatment, at first treatment and annually to Year 3 post-treatment. Principal component analysis (PCA) and redundancy analysis assessed whether any AKUSSI features contributed little information to the overall score.

Results: 65 AKU patients were included: 17 with a pre-treatment AKUSSI measurement (10 later received nitisinone) and 48 with a first measurement at their first treatment visit. In PCA, the first four principal components (PC1–PC4) explained ≥50% of AKUSSI variance at all visits (54.1–87.3%). Some features regularly dominated their domain’s PC1: ears, aortic sclerosis, and nasal/temporal eye scores (clinical), pain-related scores (joint) and cervical, lumbar and thoracic spine scores (spine). Only the right-hand/wrist score was consistently redundant. Right eye (nasal) and left ear scores were redundant pre-treatment, potentially correlating with other dominant clinical PC1 features.

Conclusions: PCA and redundancy analysis supported the AKUSSI as a robust AKU disease severity measure, although some AKUSSI features could be removed for simplicity. For small patient populations and rare diseases, PCA and redundancy analysis together can aid validation of disease severity metrics.


Alkaptonuria Assessment Efficacy Nitisinone Ochronosis Severity 



We would like to acknowledge and thank Robert Gregory who founded the AKU Society. The National AKU Centre is funded by the NHS England Highly Specialised Services and is hosted by the Royal Liverpool University Hospital. The authors thank all those who contributed to this study including the multidisciplinary team at the Royal Liverpool University Hospital for data generation, and the patients with AKU who participated in research at the National AKU Centre and gave permission for their data to be used.

Supplementary material

472895_1_En_98_MOESM1_ESM.docx (50 kb)
Supplementary Table S1 Features of each domain of the AKUSSI (DOCX 50 kb)


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Bryony Langford
    • 1
    Email author
  • Megan Besford
    • 1
  • Aimée Hall
    • 1
  • Lucy Eddowes
    • 1
  • Oliver Timmis
    • 2
  • James A. Gallagher
    • 3
  • Lakshminarayan Ranganath
    • 4
  1. 1.Costello MedicalCambridgeUK
  2. 2.AKU SocietyCambridgeUK
  3. 3.Department of Musculoskeletal BiologyUniversity of LiverpoolLiverpoolUK
  4. 4.Royal Liverpool University HospitalLiverpoolUK

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