UNASSIGNED: Wilson disease is an autosomal recessive disorder owing to defective copper metabolism which causes abnormal accumulation of copper and damage to the liver, brain, kidneys and other organs.
UNASSIGNED: To describe the clinical features, laboratory investigations and outcome of Wilson disease in children.
UNASSIGNED: A retrospective observational study was conducted in the paediatric department of a tertiary- care hospital in South India by reviewing medical records between January 2018 and March 2023. The diagnosis of Wilson disease was confirmed by the presence of low serum ceruloplasmin and/or high urine copper excretion in combination with clinical and ophthalmological features.
UNASSIGNED: A total of 32 cases were analysed. The mean (SD) age at presentation was 110 (36) months with a M:F ratio of 1.6:1. Isolated hepatic involvement was seen in 19 (60%) patients while 13 (40%) patients had a neurological presentation, either as an isolated entity or in combination with hepatic manifestations. Low serum ceruloplasmin levels were detected in 31 (96%) patients. Urine copper levels were elevated in all patients. Twenty-one patients were commenced on D penicillamine while 11 patients were treated with a combination chelation therapy with zinc. Eighteen patients (56%) were on regular follow-up.
UNASSIGNED: The clinical presentation of Wilson disease in children is diverse, varying from the more common hepatic or neurological manifestations to the less common atypical forms of the disease. Diagnosis is based on clinical and ophthalmological features in combination with biochemical abnormalities in the form of low ceruloplasmin and high urinary copper. The majority of patients can be medically managed with chelation therapy.

OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease.
METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease.
RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period.
CONCLUSIONS: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.

UNASSIGNED: Reduction of the production of amyloid-β (Aβ) species has been intensively investigated as potential therapeutic approaches for Alzheimer\'s disease (AD). However, the degradation of Aβ species, another potential beneficial approach, has been far less explored.
UNASSIGNED: To investigate the potential of multi-copper oxidases (MCOs) in degrading Aβ peptides and their potential benefits for AD treatment.
UNASSIGNED: We investigated the degradation efficiency of MCOs by using electrophoresis and validated the ceruloplasmin (CP)-Aβ interaction using total internal reflection fluorescence microscopy, fluorescence photometer, and fluorescence polarization measurement. We also investigated the therapeutic effect of ascorbate oxidase (AO) by using induced pluripotent stem (iPS) neuron cells and electrophysiological analysis with brain slices.
UNASSIGNED: We discovered that CP, an important MCO in human blood, could degrade Aβ peptides. We also found that other MCOs could induce Aβ degradation as well. Remarkably, we revealed that AO had the strongest degrading effect among the tested MCOs. Using iPS neuron cells, we observed that AO could rescue neuron toxicity which induced by Aβ oligomers. In addition, our electrophysiological analysis with brain slices suggested that AO could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus.
UNASSIGNED: To the best of our knowledge, our report is the first to demonstrate that MCOs have a degrading function for peptides/proteins. Further investigations are warranted to explore the possible benefits of MCOs for future AD treatment.

Wilson\'s disease is a rare genetic disorder characterized by abnormal copper metabolism due to mutations in the ATP-7B gene. This case report details the presentation of a 14-year-old male child exhibiting severe generalized dystonia, rigidity, myoclonic jerks, dysarthria, and excessive salivary drooling. During ophthalmic examination, Kayser-Fleischer rings were identified. Symmetrical hyperintensities in cortical and subcortical areas, including the basal ganglia and brainstem, were noted on brain magnetic resonance imaging (MRI). Additionally, diffusion restriction in the bilateral fronto-parietal region was observed. The diagnosis of Wilson\'s disease was confirmed through further diagnostic assessments, such as serum ceruloplasmin levels and urine copper excretion. Treatment was initiated with penicillamine, anticonvulsants, and supportive measures, resulting in partial recovery after a three-month follow-up period. This case emphasizes the significance of identifying atypical MRI brain findings in Wilson\'s disease, which aids in early diagnosis and appropriate management to prevent irreversible neurological damage.

Aceruloplasminemia (ACP) is a rare genetic disorder that manifests in adulthood due to mutations in the CP (ceruloplasmin) gene, causing iron accumulation and neurodegeneration. Clinically, ACP presents with a range of symptoms, including mild microcytic anemia, diabetes mellitus, liver disease, retinopathy, progressive neurological symptoms such as cerebellar ataxia, involuntary movements, parkinsonism, mood and behavior disorders, and cognitive impairment. We present the case of a 53-year-old female with a history of first-degree consanguinity and a sister with anemia. At six years old, she developed asthenia, leading to multiple hospitalizations for acute hemolytic anemia requiring transfusions and iron therapy. She exhibited later memory disturbances, slowed comprehension, social withdrawal, and school discontinuation. At the age of 51, she developed gait disturbances, unexplained falls, and cognitive decline. One year later, cranial CT revealed a chronic bilateral subdural hematoma. On admission at 53, she had anarthria, right hemiparesis, diffuse rigidity, mouth dystonia, oculomotor paralysis, and intellectual deterioration. MRI showed superficial cortical and leptomeningeal hemosiderin deposits and bilateral signal anomalies in various deep brain regions. EEG revealed paroxysmal anomalies and abdominal MRI indicated hepatic iron overload. Laboratory tests confirmed ACP. This case highlights the rare and severe neurological and systemic manifestations of ACP, emphasizing the importance of early diagnosis and intervention in such degenerative diseases to prevent irreversible neurological complications.

BACKGROUND: Wilson\'s disease (WD) is a rare autosomal recessive disease that causes impaired copper circulation and excretion. The initial manifestations of WD vary clinically, which makes early diagnosis very difficult. Sleep disorders have been described as common symptoms of WD, but the initial manifestations are in rare cases.
METHODS: This study aims to present a patient with acute insomnia as the initial manifestation of WD. Cranial magnetic resonance imaging showed extensive lesions in the bilateral putamen and caudate nucleus, pressure area of corpus callosum, midbrain, and pons. Interestingly, rare but characteristic signs of WD, such as \"face of the giant panda,\" were shown in this case. WD diagnosis was further established by decreased ceruloplasmin level and ATP7B (adenosine-triphosphatase copper transporting beta polypeptide) gene mutations.
CONCLUSIONS: We describe acute insomnia as the initial manifestation of WD in a 21-year-old male patient. Timely diagnosis allows for early copper-eliminating pharmacotherapy, which is of high prognostic importance, as the patient may be more responsive to treatment at this point.

A female adolescent presented with a 9 month history of progressive involuntary movements, initially manifesting as finger tremors and evolving into flinging motions of the extremities, resulting in an inability to walk over the last 4 months. Concurrently, she developed dysarthria. Neurologically, she exhibited normal power, rigidity and brisk deep tendon reflexes, with a downgoing plantar reflex. Contrast-enhanced MRI revealed hyperintensity in bilateral caudate lobes, basal ganglia and pons, indicative of Wilson\'s disease. Liver function tests and ultrasound were normal while Kayser-Fleischer rings were confirmed by slit lamp examination. Serum ceruloplasmin was low, 24-hour urine copper was elevated (125.5 mcg) and whole exome sequencing identified a heterozygous ATP7B mutation, confirming the diagnosis. Isolated neurological involvement without hepatic involvement is an extremely rare presentation and needs clinical expertise to delineate Wilson\'s disease as a possible aetiology.

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OBJECTIVE: Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed and applied to a cohort of 71 patients, as part of a Wilson Disease Registry Study.
METHODS: Elemental copper-protein speciation was developed for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. The serum proteins were separated using gradient elution and measured at m/z 63 (63Cu+) and 48 (32S16O+) using oxygen reaction mode and Cu-EDTA as calibration standard. The ANCC was calculated by subtraction of the ceruloplasmin bound copper from the total serum copper and the RelANCC was the percentage of total copper present as the ANCC.
RESULTS: The accuracy of the holo-ceruloplasmin measurement was established using two certified reference materials, giving a mean recovery of 94.2 %. Regression analysis between the sum of the copper containing species and total copper concentration in the patient samples was acceptable (slope=0.964, intercept=0, r=0.987) and a difference plot, gave a mean difference for copper of 0.38 μmol/L. Intra-day precision for holo-ceruloplasmin at serum copper concentrations of 0.48 and 3.20 μmol/L were 5.2 and 5.6 % CV and the intermediate precision at concentrations of 0.80 and 5.99 μmol/L were 6.4 and 6.4 % CV, respectively. The limit of detection (LOD) and lower limit of quantification (LLOQ) for holo-ceruloplasmin were 0.08 and 0.27 μmol/L as copper, respectively.
CONCLUSIONS: ANCC and Relative ANCC are important new diagnostic and monitoring biomarker indices for Wilson disease (WD).

OBJECTIVE: This study aimed to illustrate the copper status of diminished ovarian reserve in Chinese women, especially the effects of copper, ceruloplasmin, non-ceruloplasmin-bound copper (NCC) and CuZn superoxide dismutase (SOD1).
METHODS: This case-control, cross-sectional investigation included women with diminished ovarian reserve (DOR group, n = 35) and matched normal ovarian reserve (NOR group, n = 35). The serum levels of copper, ceruloplasmin, NCC, SOD1, follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, and anti-Müllerian hormone were tested and analyzed.
RESULTS: The serum copper concentrations (60.88%), NCC (54.75%) and SOD1 (54.75%) in the DOR group were significantly higher than those in the NOR group (all P < 0.001), and the concentrations of the three markers were higher in most subgroups (P < 0.001). The correlation analysis verified the correlation between copper status and impaired ovarian function. Additionally, linear regression analysis showed that NCC and SOD1 levels were negatively correlated with anti-Müllerian hormone (P < 0.05 or 0.001).
CONCLUSIONS: Our exploration found significant increases in copper, NCC and SOD1 levels in DOR and suggests a possible link. Copper status is expected to serve as the predictive marker for DOR.