Wilson disease in Costa Rica: Pediatric phenotype and genotype characterization

Abstract

Introduction The prevalence of Wilson disease (WD) in Costa Rica is among the highest reported in the world, 4.9:100 000. Previous investigators have also described a burden of autosomal recessive conditions in this country. Genetic testing for WD began in 2010 as a strategy for earlier detection due to the country's high prevalence. Here we describe what we have learned about the genotype and phenotype of the Costa Rican pediatric population with WD. Methods We completed a retrospective review of medical records from pediatric individuals (<18 years of age) with molecular testing for ATP7B between 2010 and 2015. We documented phenotype and genotype for cases with WD as defined by the international scoring system. Results Thirty‐four WD cases from 28 families were included, 15 female and 19 male patients. The most frequent pathogenic variant in ATP7B was NM_000053:c.3809A>G, p.Asn1270Ser, with 58.8% of affected individuals homozygous for this variant. Age of diagnosis ranged from 1 to 17 years, with an average of 8.8 ± 3.6 years. All individuals who presented with acute liver failure (n = 6) were homozygous for the p.Asn1270Ser variant (Chi‐squared, P < .05). Discussion Molecular testing has facilitated the detection of presymptomatic patients with WD in Costa Rica. We hope that ongoing efforts in the delivery of clinical services lead to optimized molecular screening for WD and other genetic conditions in Costa Rica.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Wilson’s disease is a “National Interest Disease”, which ensures treatment and management of patients in the Costa Rican Social Security National Health System. Researchers have recently reported genotype and phenotype data on Wilson’s disease in Costa Rican pediatric patients [ 1197 ]. Finally, a pilot in 20 collection facilities (of over 1000) has also been implemented to improve and standardize the transport of specimens from collection facilities to the central screening laboratory [ 1198 ].…”

Wilson Disease Prevalence

“…Founder mutations were evident in both the Gran Canaria and the Spanish populations. The p.Leu708Pro allele reveals a history of isolation and emigration: amplified in the population of Gran Canaria, where it probably originated (31), and spread to American territories where islanders have migrated for centuries (41–44). Meanwhile, the p.Met645Arg mutation, well represented in both the Canary archipelago and mainland Spain, shows its highest frequency in Ashkenazi Jews (30).…”

Neurological-Type Wilson Disease: Epidemiology, Clinical Manifestations, Diagnosis, and Management

“…Several regions statistically display higher rates of WD among their population, including Germany, Japan, and Austria [ 3 ]. However, the region with the highest incidence of WD in the world is Costa Rica, reporting a rate of 4.9/100000 inhabitants [ 3 , 6 ]. Their incidence rate is attributed to increased consanguinity within the country [ 3 , 6 ].…”

“…However, the region with the highest incidence of WD in the world is Costa Rica, reporting a rate of 4.9/100000 inhabitants [ 3 , 6 ]. Their incidence rate is attributed to increased consanguinity within the country [ 3 , 6 ]. The most common mutation linked to WD in Europe and North America is p.H1069Q [ 5 ].…”

“…The diagnosis of neurological-type WD is difficult due to the diverse neurological manifestations it can present with. The most notable symptom is a tremor which occurs in up to 55% of patients on the initial encounter and is present in about 90% of patients during the duration of the disease [ 6 ]. Contemporary literature has reported a delay of diagnosis from the onset of its first symptom by 2.5-6 years [ 8 ].…”