Urological complications and copper replacement therapy in childhood Menkes syndrome

Background: Urological complications are frequent in Menkes syndrome, a very rare X-linked recessive disorder of copper (Cu) metabolism. Aim: To evaluate the role of Cu therapy in preventing the progression of urological complications. Subjects and methods: We retrospectively enrolled 57 patients with Menkes syndrome (55 published case reports and two of our own unpublished cases) and investigated the reported urological complications, distinguishing the patients with or without Cu replacement therapy and evaluating the efficacy of this therapy in the prevention of urological complications. Results: The most frequent urological complication was bladder diverticulum (38.6% of the total patients); obstruction bladder outflow and rupture of the kidney were less frequent (both 1.8% of the total). The number of congenital urological complications increased progressively by age category; in fact, 77.8% of patients did not report urological complications at the age of 0.4±0.2 y, and 28.6% of them displayed ≥ two congenital urological complications at the age of 9.3±2.6 y. The percentage of urological complications found in younger patients not on Cu therapy did not differ from that of older patients treated with Cu therapy. A comparison between patients of the same age interval, who were or were not treated with Cu, showed that treated children had fewer urological complications than untreated children. Conclusion: Our investigation suggests that Cu therapy in patients with Menkes syndrome does not prevent the progression of urological complications; however, it might delay their worsening.