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

J Paediatr Child Health. 2021 Apr;57(4):519-525. doi: 10.1111/jpc.15250. Epub 2020 Dec 30.

PMID: 33377563

Charles M Lourenço, Andre Pessoa, Carmen C Mendes, Carolina Rivera-Nieto, Diane Vergara, Mónica Troncoso, Emily Gardner, Francisca Mallorens, Lina Tavera, Luis A Lizcano, Nora Atanacio, Norberto Guelbert, Norma Specola, Nury Mancilla, Carolina F M de Souza, Sara E Mole

Summary: The data of this study support the inclusion of neuronal ceroid lipofuscinosis type 2 (CLN2) disease, in the differential diagnosis of children who have seizures, behavioural disorders, or language abnormalities. Early diagnosis will allow early initiation of specific treatments.

Abstract:

Aim: Neuronal ceroid lipofuscinosis type 2 (CLN2) disease, is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency, which causes progressive deterioration of neurological functioning in children aged 2–4 years and results in early death. Atypical cases have already been reported, including those with earlier or later symptom onset, or even protracted course. Such a wide range of symptoms can make early identification and treatment even more difficult. The goal of this study was to examine clinical data from a cohort of CLN2 patients from Latin America who had unusual phenotypes.

Methods: According to the current literature on this topic and their clinical experience, experts in inborn errors of metabolism from Latin America picked patients from their centers who were regarded by the doctors to have atypical forms of CLN2. Clinical and genetic data from medical records were re-examined retrospectively. At an Advisory Board Meeting in Sao Paulo, Brazil, in October 2018, these experts presented and analyzed all of the cases.

Results: The initial signs of the late infantile type were seizures, linguistic problems, and behavioural issues, which appeared at a median age of 6 years, which is older than the age traditionally associated with the late infantile form. Three novel mutations were identified as well.

Conclusion: The data of this study support the inclusion of CLN2 in the differential diagnosis of children who have seizures, behavioural disorders, or language abnormalities. Early diagnosis will allow early initiation of specific treatments.