Akademik Veri Yönetim Sistemi
International Congress of Inborn Errors of Metabolism (ICIEM) 2025, Kyoto, Japonya, 2 - 06 Eylül 2025, (Yayınlanmadı)
Introduction
Alkaptonuria (AKU) is an inborn error of metabolism occurring due to the deficiency of homogentisate 1,2-dioxygenase(HGD) enzyme. Deficiency of this enzyme results in the accumulation of homogentisic acid (HGA).
An 80-year-old female with a long-standing diagnosis of ankylosing spondylitis since the age of 50 presented with progressive musculoskeletal pain and restricted mobility under treatment regimen included methotrexate, adalimumab, ibandronic acid. She reported significant limitations in ambulation and posture due to chronic joint pain affecting the upper and lower extremities and lumbar region. The patient had undergone bilateral total hip arthroplasty at ages 74, during which ochronotic pigment deposits were observed in the articular cartilage. Notably, the patient reported lifelong darkening of urine, which she considered normal due to similar findings in her first-degree cousin (also her spouse) and her three children.
Physical examination revealed characteristic bluish-black pigmentation of the sclerae and auricles.Transthoracic echocardiography demonstrated regurgitation of the tricuspid, mitral, and aortic valves, along with aortic valve calcification.
Dual-energy X-ray absorptiometry revealed osteopenia Urinary organic acid analysis demonstrated markedly elevated HGA excretion (397 mmol/mol creatinine).
Genetic testing confirmed a homozygous pathogenic variant in the HGD gene(c.586A>C). Given her advanced age, therapy was initiated with a low dose of nitisinone (1 mg/day) with dietary protein restriction. Remarkably, urine discoloration resolved within the first week of therapy. The patient also reported a significant reduction in musculoskeletal pain within the first month of treatment. Biochemical follow-up revealed a greater than 90% reduction in urinary HGA excretion.
Discussion and Conclusion:
Although alkaptonuria is not typically life-limiting, it significantly compromises quality of life due to chronic pain, mobility limitations, and multisystem complications.
Early diagnosis and intervention are emphasized in the management of most inborn errors of metabolism; however, this case demonstrates the potential benefits of initiating treatment even at an advanced age. The patient's positive clinical and biochemical response to low-dose nitisinone underscores the efficacy of therapy in elderly individuals.
This case represents the oldest known patient to begin nitisinone treatment and highlights the importance of clinical vigilance and intervention regardless of patient age