Alkaptonuria: pathogenesis, clinical manifestations, and management perspectives
DOI:
https://doi.org/10.33974/jjj9az89
Keywords:
Alkaptonuria , Homogentisic acid, Ochronosis, Nitisinone, ArthropathyAbstract
Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by mutations in the HGD gene, leading to deficiency of homogentisate 1,2-dioxygenase and accumulation of homogentisic acid (HGA). Oxidized HGA forms ochronotic pigment that deposits in connective tissues, producing progressive damage. The earliest sign is urine darkening. Over time, bluish-brown discoloration of cartilage, spinal stiffness, large-joint arthritis, tendon ruptures, aortic valve disease, and renal calculi may develop. The global prevalence ranges from 1 in 25,000 to 1 in 1,000,000 births, with higher incidence in Slovakia, the Dominican Republic, India, and Jordan. Diagnosis is confirmed by urinary HGA measurement via high-performance liquid chromatography, HGD mutation analysis, and imaging such as MRI, CT, or DEXA.Treatment is mainly supportive, including analgesics, physiotherapy, and surgery for severe joint involvement. Nitisinone therapy significantly reduces urinary HGA and may slow disease progression but requires monitoring of plasma tyrosine levels. Although AKU rarely reduces lifespan, it causes substantial morbidity, highlighting the importance of early detection, multidisciplinary management, and further research into disease-modifying therapies.
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