Abstract
BackgroundCommonly 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.ObjectiveTo 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.MethodsDNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records.ResultsNine 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.ConclusionsThis 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.
Highlights
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, progressive neurodegeneration, and neurological symptoms
This investigation supports that the previously characterized c.214G > T mutation is the most com‐ mon 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 Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) NCL patients in other geographies
After obtaining approval from the Institution’s Scientific Ethics Committee (CEC-CENTRAL-Costa Ricas Social Security System (CCSS)) and authorization from the Director of Costa Ricas National Childrens Hospital (HNN), the parents of all patients with a clinical diagnosis of Batten disease currently treated at the Costa Rica’s National Children’s Hospital (HNN) Neurology Department were contacted, the study was explained and the investigators invited the parents so their child could participate
Summary
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. Neuronal ceroid lipofuscinoses (NCLs) constitute a group of genetic neurodegenerative diseases associated with motor and cognitive regression; progressive cortical, thalamic, and cerebellar atrophy; retinopathy; epilepsy; and a shortened lifespan [1, 2]. NCLs causative mutations have been mapped to at least 13 different genes, which encode a diverse set of lysosomal enzymes, cytosolic chaperones, and transmembrane proteins with roles in secretory and endolysosomal trafficking [3]. Slight variations in the clinical course of CLN6 disease have been linked to the causative mutations and the country of origin [20]
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