Stem cells treatment for wilson disease

: Wilson disease (WD) is a copper excretion disorder, mainly caused by mutations in the ATP7B gene. Pharmacological therapies and liver transplantation are currently the main treatment methods for WD, but they face problems such as drug treatment compliance, adverse reactions, and shortage of liver donors. Stem cell therapy of WD may correct abnormal copper metabolism permanently, which is the focus of current research. In this review, we summarized the latest research on stem cells treatment for WD, as well as current challenges and future expectations.

Copper Imbalance in Alzheimer’s Disease: Meta-Analysis of Serum, Plasma, and Brain Specimens, and Replication Study Evaluating ATP7B Gene Variants

Evidence indicates that patients with Alzheimer’s dementia (AD) show signs of copper (Cu) dyshomeostasis. This study aimed at evaluating the potential of Cu dysregulation as an AD susceptibility factor. We performed a meta-analysis of 56 studies investigating Cu biomarkers in brain specimens (pooled total of 182 AD and 166 healthy controls, HC) and in serum/plasma (pooled total of 2929 AD and 3547 HC). We also completed a replication study of serum Cu biomarkers in 97 AD patients and 70 HC screened for rs732774 and rs1061472 ATP7B, the gene encoding for the Cu transporter ATPase7B. Our meta-analysis showed decreased Cu in AD brain specimens, increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples, and unchanged ceruloplasmin. Serum/plasma Cu excess was associated with a three to fourfold increase in the risk of having AD. Our replication study confirmed meta-analysis results and showed that carriers of the ATP7B AG haplotype were significantly more frequent in the AD group. Overall, our study shows that AD patients fail to maintain a Cu metabolic balance and reveals the presence of a percentage of AD patients carrying ATP7B AG haplotype and presenting Non-Cp Cu excess, which suggest that a subset of AD subjects is prone to Cu imbalance. This AD subtype can be the target of precision medicine-based strategies tackling Cu dysregulation.

Wilson Disease in Children: Diagnosis and Management Update

Wilson disease is an autosomal recessive, copper storage disease, caused by a mutation in the ATP7B gene. Due to mutation in ATP7B is decreased secretion of ceruloplasmin into blood and decrease in excretion of copper into bile. Excess copper accumulate to toxic levels,mainly in the liver and secondarily in other organs. Children clinically become symptomatic after the age of 5 years. Clinical features ranges from asymptomatic raised transaminases to variable degree of liver disease, neurological symptoms and according involvement of other oragns. Diagnosis of Wilson disease is challenging. Modified Leip-zig score is useful for diagnosis. Treatment can be done with zinc and other chelators. KYAMC Journal Vol. 11, No.-4, January 2021, Page 212-217

Wilson’s Disease with Hepatogenous Diabetes: A Case Report

Introduction: Wilson’s disease (WD) is a hereditary autosomal recessive disorder caused by pathogenic variants within the ATP7B gene. Early diagnosis of WD is important but it can be difficult in pediatric clinical practice because of varied presentations. Fortunately, with the development of genetic testing, molecular analysis of the ATP7B gene is helpful in the early diagnosis of WD. Hepatogenous diabetes (HD) is defined as a state of impaired glucose regulation caused by chronic liver disease. Here we report a child with WD with HD. Case Presentation: A 4-year-old girl was admitted to our hospital with diarrhea for two months. On admission, urine glucose was 4+, fasting glucose was 2.6 mmol/L, and postprandial blood glucose was 7.2 mmol/L. Further clinical manifestations and laboratory tests showed coagulation dysfunction, hemolytic anemia, and cirrhosis. After admission, she developed hepatic encephalopathy. Significant abnormal glucose metabolism was later detected, but by then, hypoglycemic convulsions had taken place. The final diagnosis of WD was confirmed by detection of mutations in the ATP7B gene. Genetic sequencing revealed compound heterozygous mutations in ATP7B, including c.2975C > T, p.Pro992Leu and c.3809A > G, p.Asn1270Ser. On day 40 of admission, the patient underwent successful orthotopic liver transplantation. Her liver function, blood glucose levels, and coagulation test results returned to normal one month after the liver transplantation. The symptom of diarrhea was also relieved after surgery. Her abnormal glucose level in hospital was considered to be HD. Conclusions: Blood glucose levels must be carefully monitored in Wilson’s disease. Moreover, genetic sequencing provides an accurate and minimally invasive diagnostic tool for WD.

A Novel Mutation of ATP7B Gene in a Case of Wilson Disease

Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes. It is a rare disorder that occurs in approximately 1 in 30,000 individuals. The clinical presentations of WD are highly varied, primarily consisting of hepatic and neurological conditions. WD is caused by homozygous or compound heterozygous mutations in the ATP7B gene. The diagnosis of the disease is complicated because of its heterogeneous phenotypes. The molecular genetic analysis encourages early diagnosis, treatment, and the opportunity to screen individuals at risk in the family. In this paper, we reported a case with a novel, hotspot-located mutation in WD. We have suggested that this mutation in the ATP7B gene might contribute to liver findings, progressing to liver failure with a loss of function effect. Besides this, if patients have liver symptoms in childhood and/or are children of consanguineous parents, WD should be considered during the evaluation of the patients.