Abstract

Alkaptonuria, a rare metabolic disorder caused by a deficiency in homogentisate 1,2-dioxygenase, leads to the accumulation of homogentisic acid (HGA) and subsequent deposition of ochronotic pigment in connective tissues. The clinical manifestations of alkaptonuria include musculoskeletal issues, such as arthritis and spinal involvement, along with cardiovascular complications. Historically, management strategies for alkaptonuria focused on symptomatic relief; however, the advent of nitisinone has revolutionized treatment paradigms. Nitisinone, a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the enzyme upstream of the metabolic block in alkaptonuria, has shown promising results in reducing urinary HGA excretion and slowing disease progression. This review aims to summarize the current evidence regarding the effectiveness and safety of nitisinone in managing alkaptonuria. We conducted a thorough literature search of PubMed, Embase, and relevant databases, identifying clinical trials, observational studies, and case reports investigating the use of nitisinone in alkaptonuria. The review encompasses data on nitisinone dosing regimens, biochemical responses, clinical outcomes, and adverse events reported in patients with alkaptonuria.

Preliminary findings suggest that nitisinone effectively decreases urinary HGA levels, thereby mitigating ochronosisrelated symptoms and preserving joint function. Furthermore, long-term studies indicate a potential diseasemodifying effect of nitisinone, with some patients experiencing stabilization or even improvement in musculoskeletal manifestations. However, challenges such as optimal dosing, treatment duration, and long-term safety profiles warrant further investigation. In conclusion, nitisinone holds promise as a therapeutic cornerstone in the management of alkaptonuria, offering a novel approach to attenuate disease progression and improve clinical outcomes. Continued research efforts are essential to elucidate the optimal use of nitisinone and its role in comprehensive care strategies for individuals with alkaptonuria.