Urological Problems in Patients with Menkes Disease

Abstract

BackgroundMenkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic “kinky” hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. In this study, we studied the clinical features and outcomes of MD, focusing on urological complications.MethodsA total of 14 unrelated Korean pediatric patients (13 boys and 1 girl) with MD were recruited, and their phenotypes and genotypes were analyzed by retrospective review of their medical records.ResultsAll the patients had early-onset neurological deficit, including developmental delay, seizures, and hypotonia. The girl patient showed normal serum copper and ceruloplasmin levels as well as milder symptoms. Mutational analysis of the ATP7A gene revealed 11 different mutations in 12 patients. Bladder diverticula was the most frequent urological complication: 8 (57.1%) in the 14 patients or 8 (72.7%) in the 11 patients who underwent urological evaluation. Urological imaging studies were performed essentially for the evaluation of accompanying urinary tract infections. Four patients had stage II chronic kidney disease at the last follow-up.ConclusionUrologic problems occurred frequently in MD, with bladder diverticula being the most common. Therefore, urological imaging studies and appropriate management of urological complications, which may prevent or reduce the development of urinary tract infections and renal parenchymal damage, are required in all patients with MD.

Copper chelation therapy inhibits renal fibrosis by modulating copper transport proteins

“…Although the direct contribution of Cu in fibrosis induction involving LOX proteins has not been established, there are reports suggesting that there is a definite involvement of dysregulation of Cu homeostasis in the kidney disease 16,17 . In addition, the pathophysiological basis of Menke's and Wilson's disease also point toward the association of dysregulated Cu pathway with these diseases 18–20 . Due to critical role of Cu homeostasis in kidney physiology, the present study tried to investigate the contribution of Cu overload in renal fibrosis by focusing on Cu transporters and LOX enzymes.…”

Tubular Dysfunction and Ruptured Ureter in a Child with Menkes Syndrome

“…Children with Menkes disease may develop various urological abnormalities, and bladder diverticulum is the most frequently reported one, with a reported prevalence ranging from 36.8% to 57.1% [ 2 , 3 ]. Lysyl oxidase is a copper-dependent and elastic-fiber-associated coenzyme responsible for lysine-derived cross-linking of collagen and elastin in connective tissue.…”

“…Most patients have severe developmental delay, seizures, failure to thrive, and connective tissue abnormality resulting in blood vessel tortuosity and the characteristic kinky hair [ 1 ]. Besides, urological abnormalities and related complications such as recurrent urinary tract infection may also be encountered [ 2 , 3 ]. We report a 4-year-old boy with Menkes disease who presented with urosepsis, and subsequent workup identified a ruptured right ureter resulting from a ureteric stone.…”

Bladder Diverticula Caused by Occipital Horn Syndrome: A Case Report

“…One Korean study showed that urological problems occurred frequently in Menkes disease, with bladder diverticula being the most common (11). Bladder diverticula result in urinary stasis with a high residual urine volume, which leads to UTIs.…”