Musculoskeletal findings and disability in alkaptonuria

Objective. To describe the musculoskeletal (MSK) findings in patients with alkaptonuria and to show which of these factors are associated with disability in this population. Methods. This is a prospective cross-sectional MSK assessment of subjects. Participants included 53 patients with alkaptonuria across the life span, 22 female and 31 male, mean age 43.6 years (10-80 yrs), participating in a natural history study supported by the National Human Genome Research Institute (NHGRI). Assessments included objective measures of the MSK system (range of motion, radiographic assessment of joints and spine, etc.) and questionnaires including the Human Activity Profile (HAP), Health Assessment Questionnaire (HAQ), SF-36 health survey, and the Fatigue Assessment Instrument. Results. There were 18 patients with kyphosis, 16 with scoliosis, 16 with marked reduction in range of motion of at least one major joint, 15 with joint replacements of major joints, 11 with tendon ruptures. A positive Schober's test was highly correlated with substantial functional loss and associated with disability as measured by the HAP (p < 0.0001), HAQ (p < 0.0001), and the physical component summary (p < 0.0001) of the SF-36 health survey. Severity of lumbar spine involvement had the greatest correlation with disability measures (p < 0.0001). All objective and subjective physical measures worsened with age. Conclusion. Disability is common and severe in patients with alkaptonuria and correlates well with physical findings. Disability does not correlate with self-reports of mental competencies. Aging with alkaptonuria is associated with progressive disability.