Wilson's disease in two siblings from Ecuador:Two case reports

BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and cornea.Diagnoses and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are limited.Prompt diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life expectancy.The clinical presentations and outcomes of WD can vary within a single family.CASE SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family screening.The male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer rings.He developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication shortages.His condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of follow-ups.The female patient,diagnosed at age 10,exhibited only biochemical alterations.Her treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up period.We discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic strategies.CONCLUSION Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.

Characteristics of patients with Wilson disease in the United States: An insurance claims database study

BACKGROUND Wilson disease(WD)is a progressive,potentially fatal degenerative disease affecting the liver and central nervous system.Given its low prevalence,collecting data on large cohorts of patients with WD is challenging.Comprehensive insur-ance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases.AIM To describe patients with WD in the United States,their treatment and clinical outcome,using a large insurance claims database.METHODS This retrospective,longitudinal study was performed in the Clarivate Real-World Data Product database.All patients with≥2 claims associated with an Interna-tional Classification of Diseases 10(ICD-10)diagnostic code for WD(E83.01)between 2016 and 2021 were included and followed until death or study end.Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD.Clinical manifestations,hospital-isations,liver transplantation and death were documented.RESULTS Overall,5376 patients with an ICD-10 diagnostic code for WD were identified.The mean age at inclusion was 41.2 years and 52.0%were men.A specific WD treatment was documented for 885 patients(15.1%),although the number of patients taking zinc salts may be underestimated due to over the counter purchase.At inclusion,the mean age of patients with a documented treatment was 36.6±17.8 years vs 42.2±19.6 years in those without a documented treatment.During follow-up,273 patients(5.1%)died.Compared with the American general population,the standardised mortality ratio was 2.19.The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0%and the mean age at death 52.7 years.CONCLUSION Patients treated for WD in the United States had an excess early mortality compared with the American population.These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.

STUDY ON THE KINETICS OF POLYMERIZATION OF MMA BY COPPER（Ⅱ） CHELATING RESINS

The polymerization of MMA initiated by copper(Ⅱ） chelating resins/CCl4 system was studied.From the kinetic data,the kinetic equation of polymerization can be expressed as Rp=Ke^-56400/RT[MMA]^1.57[CCl4]^m[RESIN-Cu]^0.18 where m:3-4.5,when[CCl4] 0.1-6.93M.The free radical polymerization mechanism is proposed.The primary radicals are formed by the process of complexation-chlorine transformation among the copper(Ⅱ) chelating resin,CCl4 and methacrylate.

Estimation of Stability Constants of Copper（Ⅱ） Complexes with a-Amino Acids Using Connectivity Index 3xV, Common Model for the Binary and Ternary Complexes

Models for estimation of the first （K1）, second （K2）, and overall stability constant （β2） of copper（II） chelates with naturally occurring amino acids, based on the valence connectivity index of the 3rd order （3Xr）, were improved by introduction of a square term and a new graph representation for mono-complexes （MLCor）. The models gave SE = 0.07, 0.05--0.07 and 0.05--0.08 for lg Ki, lg K2 and lg ,62 constants, respectively; models that encompass both bi- nary and ternary bis-complexes included indicator variable. We also validated our models on the test set which in- cluded two mono-, two binary and two ternary Cu（II） chelates with a-aminobutanoic acid and a-aminopentanoic acid, not included into the calibration. The absolute differences between experimental and predicted stability con- stants were in the range of 0.01--0.16.