Alkaptonuria is a rare autosomal recessive metabolic disorder caused by a deficiency in homogentisate 1,2-dioxygenase (HGD), leading to the accumulation of homogentisic acid (HGA) in connective tissues, cartilage, and bones. This accumulation results in multisystem involvement, including early-onset spondyloarthropathy. We present a 54-year-old female from South Tyrol with chronic back and knee pain, accompanied by typical signs of alkaptonuria: ochronosis and darkening of the urine. Molecular genetic testing confirmed the diagnosis of alkaptonuria and identified a previously unreported mutation. Following treatment with nitisinone, a protein-restricted diet, and therapy for osteoporosis, the patient showed significant improvement in symptoms. This case underscores the need to consider rare metabolic disorders in the differential diagnosis of chronic musculoskeletal pain and highlights the importance of early diagnosis and intervention for effective management. Learning points: In cases of early or unexplained degenerative spinal and joint changes in younger individuals, consider secondary metabolic causes. In the presence of the symptom triad - ochronosis, dark urine, and arthropathy - alkaptonuria should be suspected. Alkaptonuria is caused by a rare autosomal recessive defect in homogentisate 1,2-dioxygenase, leading to accumulation of homogentisic acid, which primarily results in the destruction of joints and heart valves. Diagnosis is established through biochemical testing and molecular genetic analysis of the HGD gene. Therapeutic options now include nitisinone as a causal treatment (available since 2020); however, due to often delayed diagnosis, symptomatic management and treatment of sequelae (pain control, joint care, and osteoporosis therapy) continue to play a major role.
Riegler et al. (Tue,) studied this question.