Alkaptonuria: review and cases in Portugal

Abstract

Alkaptonuria is a rare metabolic disorder that has an autosomal recessive inheritance pattern. In this disease, the enzyme homogentisate 1,2-dioxygenase is nonfunctional. This deficiency causes the accumulation of homogentisic acid in tissues and the excretion of large amounts of homogentisic acid in urine, resulting in a characteristic triad of clinical features: homogentisic aciduria (alkaptonuria), ochronosis (pigmentation of the tissues), and ochronotic arthropathy. The ochronotic arthropathy mostly affects the thoracolumbar spine and the large joints, like the shoulders, knees, and hips. It causes severe pain and stiffness, which leads to functional disability. In the absence of a highly effective etiological therapeutic option, treating patients suffering from ochronotic arthropathy remains extremely difficult. The therapeutic approach is often limited to symptomatic treatment and, in some cases, the placement of joint prostheses. In September 2020, the European Medicines Agency approved the use of nitisinone in the treatment of alkaptonuria. Patient organizations are relevant and may be useful to help in the education and support of patients and their families, as well as for therapeutic purposes. Despite its rarity, alkaptonuria occurs in Portugal. This review presents some patient cases and a post-mortem examination. Through the analysis of the cases presented, it was concluded that alkaptonuria is an underdiagnosed or late-diagnosed disease in Portugal that requires more disclosure to ensure an early diagnosis and the onset of treatment, which may increase the quality of life. The goal of this work is to divulge information about alkaptonuria to bring awareness about this disease, increase research and diagnosis, and ultimately allow the patients to get access to the right health care in order to improve their quality of life.