Wilson disease in children and young adults - State of the art

Abstract

Wilson disease (WD) is an autosomal recessive disorder caused by mutations of the ATP7B gene, with a reported prevalence of 1:30,000–50,000. ATP7B encodes an enzyme called transmembrane copper-transporting ATPase, which is essential for copper incorporation into ceruloplasmin and for copper excretion into the bile. A lack or dysfunction of this enzyme results in a progressive accumulation of copper in several organs, especially in the liver, the nervous system, corneas, kidneys, and heart. Children with WD can present with asymptomatic liver disease, cirrhosis, or acute liver failure, with or without neurological and psychiatric symptoms. Approximately 20%–30% of WD patients present with ALF, while most of the other patients have chronic progressive hepatitis or cirrhosis if untreated. Although genetic testing has become a more important diagnostic tool for WD, the diagnosis remains based on both clinical features and laboratory investigations. The aims of treatment are to reduce copper levels and prevent its accumulation in the liver and other organs, especially in the central nervous system. Liver transplantation in WD is a life-saving option for patients presenting with liver failure and encephalopathy. For WD patients treated with chelating agents, adherence to the therapy is essential for long-term success. In this review, we also address specific issues in young adults as compared to children.

Systemic lupus erythematosus combined with Wilson’s disease: a case report and literature review

“…Liver transplantation is a curative option because it replaces the affected liver, provides normal ATP7B protein, restores normal biliary copper excretion (preventing disease recurrence), and facilitates the removal of copper from extrahepatic sites where it may be toxic [ 29 ]. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment, who have fulminant or advanced liver failure, and/or who have significant portal hypertension [ 30 ]. With advancements in liver transplantation technology, the clinical indications for WD patients receiving liver transplantation have expanded, leading to satisfactory outcomes.…”

Enfermedad de Wilson: de la clínica a la genética

“…El cobre ingresa a los hepatocitos a través del transportador de cobre 1 (CTR1) para llegar a la red trans Golgi a través de ATP7B, donde se incorpora a la apoceruloplasmina para formar holoceruloplasmina, la que es excretada a la circulación. Cuando los niveles de cobre son excesivos, ATP7B se redistribuye a un compartimento vesicular cerca de las membranas canaliculares biliares para eliminar el exceso de cobre a través de la bilis (11,12) . Las mutaciones del gen ATP7B dan como resultado la reducción de los niveles de la proteína ATP7B y un aumento en la degradación de ésta, lo que lleva a una acumulación tóxica de cobre en el hígado y posteriormente, a un exceso de cobre no unido a ceruloplasmina en el torrente sanguíneo.…”

“…El efecto tóxico del exceso de cobre es considerado la causa primaria de los síntomas en la EW. La sobrecarga de cobre intracelular conduce al estrés oxidativo y al posterior daño oxidativo a las proteínas celulares, lípidos, ADN, ARN y mitocondrias (2,10,11) .…”

“…Las manifestaciones hepáticas varían desde hallazgos asintomáticos o incidentales como pruebas hepáticas anormales, complicaciones típicas de enfermedad hepática crónica, hasta falla hepática aguda con necesidad de trasplante (11) . En una etapa temprana, los pacientes pueden estar asintomáticos, pero se les puede encontrar incidentalmente una enzima hepática elevada o hallazgos anormales en la ecografía hepática.…”

Sorting Intolerant from Tolerant and PolyPhen-2 Algorithms: A Variation in Exon 14 of ATP7B Gene among 4 West Iraqi Families with Wilson’s Disease

“…Several studies have been conducted to investigate the implications of ATP7B gene allelic variations on the function of the ATP7B protein. There have been multiple research on the genotype-phenotype relationship within the ATP7B gene, some with favorable findings [3], and some with negative findings [4,5]. If detected early, WD is a condition that can be treated with medications, reducing morbidity and mortality.…”