Case Report: Ochronotic arthropathy mimicking spondyloarthritis: a case-based review of diagnostic pitfalls and a...

Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency, leading to pigment deposition and progressive ochronotic arthropathy (OchA), which may mimic chronic inflammatory or degenerative joint diseases and delay diagnosis.

A 48-year-old man with chronic low back pain and right knee arthritis was initially diagnosed with spondyloarthritis (SpA). Arthroscopy revealed black-brown synovial pigmentation initially overlooked. Subsequent clinical reassessment identified auricular cartilage pigmentation and progressive urine darkening, while imaging showed multilayered intervertebral disc calcification and degenerative changes, raising suspicion for AKU.

Genetic analysis detected a novel homozygous HGD missense variant (c.424A > G; p.Met142Val, exon 6), affecting a conserved residue and predicted to be deleterious. Classified as likely pathogenic according to ACMG criteria, it supported the diagnosis of OchA in conjunction with clinical, radiological and histopathological findings.

This case highlights the diagnostic challenges of OchA mimicking SpA or osteoarthritis. Recognition of progressive urine darkening, cartilage pigmentation, and multilayered disc calcification may facilitate earlier diagnosis. The novel HGD variant expands the mutational spectrum of AKU and underscores the importance of molecular testing within a multidisciplinary framework in atypical joint degeneration. Although primarily metabolic, awareness of potential inflammatory involvement may guide symptomatic management when metabolic therapy is delayed.