CLN3 DISEASE: THE CORDOBA COHORT CASUISTICS IN THE FRAME OF THE WORLD EVIDENCES

GUELBERT, GUILLERMO; CISMONDI, INÉS ADRIANA; BECERRA, ADRIANA; PESAOLA, FAVIO; VENIER, ANA CLARA; DE PAUL, ANA LUCÍA; VAZQUEZ, JUAN CARLOS G.; FERNANDEZ, ELMER; GUELBERT NORBERTO; NOHER, INÉS

St. Louis

Congreso; The 17th International Congress on Neuronal Ceroid Lipofuscinosis (NCL 2021); 2021

CLN3 disease (OMIM #204200), also known as juvenile neuronal ceroid lipofuscinosis or Batten disease is the most common Neuronal Ceroid Lipofuscinosis (NCL) in the Northern Hemisphere, and the second most common after CLN2 disease in Latin America. It is caused by DNA variants in the gene CLN3 located on chromosome 16. The gene encodes a transmembrane protein involved in lysosomal homeostasis. Studies have associated the CLN3 protein with many cellular processes. While the retinal phenotype is relatively uniform throughout the disease spectrum, it is known that the severity of mutations in CLN3 determines the neurocognitive and motor consequences of the disease. Abundant lymphocyte vacuolization in a school-aged child suffering from retinal dystrophy is pathognomonic for (classical) CLN3 disease. Aims: Observational and retrospective study of the CLN3 disease casuistic in the Cordoba cohort in the context of published evidence to offer an analytical framework for phenotypic, proteomic and genomic characterization of CLN3 disease in Latin America. Methods: the children were studied under the published algorithm of the metabolic section at the Children?s Hospital Cordoba. The clinical compatibility was assessed, mostly after a long diagnostic family odyssey. A May Grunwald Giemsa stained blood smear was obtained and at least 3% of vacuolated lymphocytes were detected under the light microscope. Electronic microscopy of a skin biopsy was observed for the detection of osmiophilic profiles in the eccrine sweet gland secretory cells. Muscle biopsies also showed the pathological bodies. Genotypes were studied with PCR followed by Sanger sequencing. Published evidences were searched for the time lapse 2011 to 2021 under the keywords CLN3 disease, Juvenile NCL, Batten disease, casuistic. The Scielo portal was screened out for Latin American literature. Results and discussion: The Cordoba cohort of CLN3 disease of 6 retrospective individuals showed mainly the classical CLN3 phenotype, being the second most abundant NCL after CLN2. 6/6 individuals had the most common 1.02kb deletion. But 3/6 in compound heterozygous combination with another DNA variant, and another 3/6 in homozygosity, differing from the world experience of more than 90% of all cases with the most common del 1,02kb (c.462_677 del) in homozygosity. This fact could be due to the high degree of mixed ethnicities in Latin America. Conclusion: Cohort studies of CLN3 in Latin America are scarce, and this type of NCL remains possibly underdiagnosed.