Abstract
Introduction: Neuronal ceroid lipofuscinoses (NCL) represent a heterogeneous group of rare neurodegenerative diseases of genetic origin that predominantly appear during childhood. To date, 14 clinical subtypes of NCL have been described according to the affected gene. NCL type 8, specifically the late infantile variant, is characterized by epileptic seizures that are difficult to control with medication, impaired gait stability, and progressive cognitive and visual impairment.
Case presentation: An 11-year-old female patient who has had epileptic seizures with a progressive onset since age 3, later presenting with instability to walk, decreased visual acuity, and cognitive impairment. The pharmacological management of epileptic seizures was unsatisfactory despite the use of multiple antiepileptic drugs in combined therapy. Gene panel for epilepsy and ataxia by next-generation sequencing (NGS), where a homozygous pathogenic variant was identified in the CLN8 gene.
Discussion: Although it was considered an entity predominantly distributed in Europe, reports include countries worldwide, including Argentina and now our case in Colombia. The clinical characteristics of the patient presented are similar to those described in the literature, given the difficult control of epileptic seizures, neurodevelopmental impairment and other neurological disorders.
Conclusions: To our knowledge, this is the first report of this entity in Colombia. Unlike other reported cases, an important factor for the late diagnosis of this entity was the limited access to genetic consultation.
References
Williams RE, Goebel HH, Mole SE, Boustany RM, Elleder A, Kohlschütter A, et al. NCL nomenclature and classification. En: Mole S, Williams R, Goebel H, editores. The Neuronal Ceroid Lipofuscinoses (Batten Disease). 2.a ed. Oxford: Oxford University Press; 2011. p. 20-23.
Nita DA, Mole SE, Minassian BA. Neuronal ceroid lipofuscinoses. Epileptic Disord. 2016;18(S2):73-88. https://doi.org/10.1684/epd.2016.0844
Specchio N, Ferretti A, Trivisano M, Pietrafusa N, Pepi C, Calabrese C, et al. Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy. Drugs. 2021;81(1):101-23. https://doi.org/10.1007/s40265-020-01440-7
Beesley C, Guerreiro RJ, Bras JT, Williams RE, Taratuto AL, Eltze C, et al. CLN8 disease caused by large genomic deletions. Mol Genet Genomic Med. 2016;5(1):85-91. https://doi.org/10.1002/mgg3.263
Ranta S, Topcu M, Tegelberg S, Tan H, Üstübütün A, Saatci I, et al. Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy. Hum Mutat. 2004;23(4):300-5. https://doi.org/10.1002/humu.20018
Reinhardt K, Grapp M, Schlachter K, Brück W, Gärtner J, Steinfeld R. Novel CLN8 mutations confirm the clinical and ethnic diversity of late infantile neuronal ceroid lipofuscinosis. Clin Genet. 2010;77(1):79-85. https://doi.org/10.1111/j.1399-0004.2009.01285.x
Cannelli N, Cassandrini D, Bertini E, Striano P, Fusco L, Gaggero R, et al. Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis: another genetic hit in the Mediterranean. Neurogenetics. 2006;7(2):111-7. https://doi.org/10.1007/s10048-005-0024-y
Allen NM, O’hIci B, Anderson G, Nestor T, Ann Lynch S, King MD. Variant late-infantile neuronal ceroid lipofuscinosis due to a novel heterozygous CLN8 mutation and de novo 8p23.3 deletion. Clin Genet. 2012;81(6):602-4. https://doi.org/10.1111/j.1399-0004.2011.01777.x
Katata Y, Uematsu M, Sato H, Suzuki S, Nakayama T, Kubota Y, et al. Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: the first report of a CLN8 mutation in Japan. Brain Dev. 2016;38(3):341-5. https://doi.org/10.1016/j.braindev.2015.09.008
Alkhars FZ, Bo Ali AY, Almohanna MA, Almajhad NA. Neuronal ceroid lipofuscinoses type 8: Expanding genotype/phenotype diversity-first report from Saudi Arabia. Neurosciences. 2020;25(1):65-9. https://doi.org/10.17712/nsj.2020.1.20190103
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.