Ochronosis – a rare metabolic disease

Alkaptonuria is a rare disorder, an autosomal recessive condition with genetic determinism and hereditary transmission, having a prevalence of 1 per 1 million population in USA. The pathogenesis includes the deficiency of the homogentisate 1,2-dioxygenase (HGD) enzyme, an intermediary enzyme in phenylalanine and tyrosine catabolism. Mutations in HGD gene leads to deficient levels of functional HGD and an excess of homogentisic acid (HGA). Although HGA is rapidly excreted by the kidneys, it slowly accumulates in various tissues. Due to HGA oxidase deficiency, HGA turns into melanin-like pigment which determines: alkaptonuria, accumulation in the connective tissues, in the joints, or can make cardiovascular and genitourinary deposits. The chronic accumulation of HGA destroys the affected tissue, leading to the characteristic black-blue color and to clinical symptoms of alkaptonuria. The aim of this paper is to investigate the particularities of rheumatic manifestations in a rare metabolic disease and to support the correct diagnosis. A 58-year-old male patient was admitted to our clinic in 2019 for bilateral knee and left shoulder pain. In 2008 he was diagnosed with polyarticular ochronosis having dorsal and lumbar pain, mixed scapulohumeral pain, lumbar intervertebral disk calcifications; at that time, a diagnosis of ankylosing spondylitis or Forestier disease was excluded. At the current admission, the patient has been thoroughly reassessed to obtain a proper diagnosis and to determine the severity of the disease. The ochronotic axial damage caused important differential diagnosis problems with ankylosing spondylitis. Pigment deposition in the eyes, ears and skin does not cause problems to patients, but cardiovascular and genitourinary deposition leads to important complications. Kinetotherapy and NSAIDs are beneficial for pain symptoms. There is no specific medication for stopping the disease progression. Conclusions. Ochronosis is a rare disease which can cause a lot of problems regarding a proper diagnosis and treatment. When differential diagnosis with AS is difficult, the HLA-B27 genotyping is recommended. Final diagnosis is based on qualitative and quantitative urinary tests. The treatment includes only symptomatic drugs such as NSAIDs and kinetotherapy to improve joint mobility and muscle toning.