Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.

BACKGROUND: Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. OBJECTIVE: To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. METHODS: DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants' sociodemographic and clinical characteristics were also obtained from their medical records. RESULTS: Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. CONCLUSIONS: This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

[Characteristics of patients with refractory epilepsy attended in a tertiary referral center in Costa Rica]. / Caracterizacion de los pacientes con epilepsia refractaria de un hospital de tercer nivel en Costa Rica.

INTRODUCTION: Thirty percent of patients with epilepsy have recurrent seizures, representing fifteen million people in the world. This population has been scarcely described. AIM: To characterize sociodemographic and clinically the patients diagnosed with refractory epilepsy in a tertiary referral hospital of the Costa Rican social security. PATIENTS AND METHODS: This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014. RESULTS: Clinical records of 91 patients were studied; patients with psychogenic seizures were analyzed separately. The mean age of onset was 13.1 ± 11.1 years, secondary generalized seizures were the predominant type (81.3%), the most frequent etiology was mesial temporal sclerosis (48.3%) and the majority had normal neurological exams and normal or low neuropsychological assessments. Around half (48.8%) of the patients had been medicated with a range of 4-6 antiepileptic drugs, being lamotrigine, carbamazepine, valproic acid and phenytoin the most prescribed. Treatment optimization, neurosurgery, and further analysis were standard recommendations. Sociodemographic characteristics, patient management, and antiepileptic drugs used are similar to the described in other latitudes. Differences between the age of onset and gender; seizure frequency and gender; age of onset and failed treatments and time of evolution of the disease and employment were observed. The percentage and characteristics of recurrent seizures of psychogenic nature found are comparable to other refractory epilepsy studies. CONCLUSION: Sociodemographic characteristics, management of patients, antiepileptic drugs used and the differences observed are similar to those previously described.

TITLE: Caracterizacion de los pacientes con epilepsia refractaria de un hospital de tercer nivel en Costa Rica.Introduccion. El 30% de los pacientes con epilepsia presenta convulsiones recurrentes, porcentaje que representa aproximadamente a 15 millones de personas en el mundo y constituye una poblacion escasamente descrita. Objetivo. Caracterizar sociodemografica y clinicamente la poblacion de pacientes diagnosticados con epilepsia refractaria en un hospital terciario de Costa Rica. Pacientes y metodos. Se analizan los registros medicos de los pacientes con epilepsia refractaria valorados en la unidad de epilepsia del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social desde agosto de 2012 a octubre de 2014. Resultados. Se incluyen los expedientes clinicos de 91 pacientes. La edad media de inicio fue de 13,1 ± 11,1 años. Las crisis secundariamente generalizadas constituyen el tipo predominante (81,3%), la etiologia mas frecuente es la esclerosis mesial temporal (48,3%) y la mayoria de los pacientes presentaba examenes neurologicos normales y valoraciones neuro­psicologicas normales o bajas. Alrededor de la mitad (48,8%) de los pacientes habia sido medicada con un rango de 4-6 farmacos antiepilepticos, y los mas prescritos fueron lamotrigina, carbamacepina, acido valproico y fenitoina. Las principales recomendaciones en estos pacientes fueron: optimizacion de tratamiento, neurocirugia y reingreso. Se observan diferencias entre la edad de inicio y el sexo, la frecuencia de las crisis y el sexo, el tiempo de evolucion de la patologia y la cantidad de tratamientos fallidos, y el tiempo de evolucion de la enfermedad y la ocupacion. Conclusiones. Las caracteristicas sociodemograficas, el manejo de los pacientes, los farmacos antiepilepticos utilizados y las diferencias encontradas son similares a las descritas en otras latitudes.