Revealing the clinical phenotype of atypical neuronal ceroid lipofuscinosis type 2 disease: Insights from the largest cohort in the world

Aim Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme, leading to progressive deterioration of neurological functions commonly occurring in children aged 2–4 ...

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Bibliographic Details
Published in:Journal of paediatrics and child health 2021-04, Vol.57 (4), p.519-525
Main Authors: Lourenço, Charles M, Pessoa, Andre, Mendes, Carmen C, Rivera‐Nieto, Carolina, Vergara, Diane, Troncoso, Mónica, Gardner, Emily, Mallorens, Francisca, Tavera, Lina, Lizcano, Luis A, Atanacio, Nora, Guelbert, Norberto, Specola, Norma, Mancilla, Nury, Souza, Carolina F M, Mole, Sara E
Format: Article
Language:English
Subjects:
Aged
Batten disease
Brazil
Child
Child, Preschool
Convulsions & seizures
Genetic disorders
Genotype & phenotype
Humans
late onset
Mutation
Neurological disorders
Neuronal Ceroid-Lipofuscinoses - diagnosis
Neuronal Ceroid-Lipofuscinoses - genetics
Original
Pediatrics
Phenotype
Retrospective Studies
seizure
TPP1 deficiency
Tripeptidyl-Peptidase 1
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Summary:Aim Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme, leading to progressive deterioration of neurological functions commonly occurring in children aged 2–4 years and culminating in early death. Atypical cases associated with earlier or later symptom onset, or even protracted course, have already been reported. Such variable manifestations may constitute an additional challenge to early diagnosis and initiation of appropriate treatment. The present work aimed to analyse clinical data from a cohort of Latin American CLN2 patients with atypical phenotypes. Methods Experts in inborn errors of metabolism from Latin America selected patients from their centres who were deemed by the clinicians to have atypical forms of CLN2, according to the current literature on this topic and their practical experience. Clinical and genetic data from the medical records were retrospectively revised. All cases were presented and analysed by these experts at an Advisory Board Meeting in São Paulo, Brazil, in October 2018. Results Seizures, language abnormalities and behavioural disorders were found as the first manifestations, appearing at the median age of 6 years, an older age than classically described for the late infantile form. Three novel mutations were also identified. Conclusion Our findings reinforce the inclusion of CLN2 in the differential diagnosis of children presenting with seizures, behavioural disorders and language abnormalities. Early diagnosis will allow early initiation of specific therapy.
ISSN:1034-4810
1440-1754
DOI:10.1111/jpc.15250