Copper metabolism in children.

F W Alexander

doi:10.1136/adc.49.8.589

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

Current Medicinal Chemistry ◽

10.2174/0929867327666200730214757 ◽

2020 ◽

Vol 27 ◽

Author(s):

Daniela Fanni ◽

Clara Gerosa ◽

Valeria Marina Nurchi ◽

Rosita Cappai ◽

Marta Mureddu ◽

...

Keyword(s):

Wilson Disease ◽

Clinical Presentation ◽

Clinical Phenotype ◽

Methylation Status ◽

Copper Metabolism ◽

Epigenetic Factors ◽

Genetic Changes ◽

Illness Onset ◽

Phenotypic Manifestation ◽

Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

Download Full-text

The Need for Consensus About Liver Transplantation For Patients With Neuropsychiatric Wilson’s Disease

Progress in Transplantation ◽

10.1177/15269248211002806 ◽

2021 ◽

pp. 152692482110028

Author(s):

Alberto Ferrarese ◽

Patrizia Burra

Keyword(s):

Liver Transplantation ◽

Patient Outcomes ◽

Wilson’S Disease ◽

Therapeutic Option ◽

Copper Metabolism ◽

Wilson's Disease ◽

Published Data ◽

Neurological Improvement ◽

Effective Therapeutic Option

Liver transplantation is considered an effective therapeutic option for Wilson’s disease (WD) patients with hepatic phenotype, since it removes the inherited defects of copper metabolism, and is associated with excellent graft and patient outcomes. The role of liver transplantation in WD patients with mixed hepatic and neuropsychiatric phenotype has remained controversial over time, mainly because of high post-operative complications, reduced survival and a variable, unpredictable rate of neurological improvement. This article critically discusses the recently published data in this field, focussing in more detail on isolated neuropsychiatric phenotype as a potential indication for liver transplantation in WD patients.

Download Full-text

Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations

Scientific Reports ◽

10.1038/s41598-021-87000-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Clemens Höflich ◽

Angela Brieger ◽

Stefan Zeuzem ◽

Guido Plotz

Keyword(s):

Wilson Disease ◽

Transcription Initiation ◽

Transcriptional Activity ◽

Core Promoter ◽

Transcriptional Start Site ◽

Copper Metabolism ◽

Biologically Relevant ◽

The Core ◽

Translational Start

AbstractPathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variability in Wilson disease patients with incompletely inactivating mutations. However, neither polymorphism significantly modulated ATP7B expression in vitro, nor were copper household parameters in healthy probands affected. In summary, the investigations allowed to determine the biologically relevant site of ATP7B transcription initiation and demonstrated that genetic variations in this site, although being the focus of transcriptional activity, do not contribute significantly to Wilson disease pathogenesis.

Download Full-text

Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

Journal of Child Science ◽

10.1055/s-0041-1731079 ◽

2021 ◽

Vol 11 (01) ◽

pp. e145-e147

Author(s):

Nida Mirza ◽

Ravi Bharadwaj ◽

Smita Malhotra ◽

Anupam Sibal

Keyword(s):

Liver Transplantation ◽

Liver Failure ◽

Acute Liver Failure ◽

Wilson Disease ◽

Prognostic Score ◽

Prognostic Index ◽

Kidney Injury ◽

Copper Metabolism ◽

Life Saving ◽

The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

Download Full-text