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. 2024 Feb 1:38:101060.
doi: 10.1016/j.ymgmr.2024.101060. eCollection 2024 Mar.

Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa

Norberto Guelbert  1 , Oscar Mauricio Espitia Segura  2 , Carolina Amoretti  3 , Angélica Arteaga Arteaga  4 , Nora Graciela Atanacio  5 , Sabrina Bazan Natacha  6 , Ellaine Doris Fernandes Carvalho  7   8 , Maria Denise Fernandes Carvalho de Andrade  7   8   9   10   11 , Inés María Denzler  12 , Consuelo Durand  13 , Erlane Ribeiro  14 , Juan Carlos Giugni  15 , Gabriel González  16 , Dolores González Moron  17 , Guillermo Guelbert  18 , Zulma Janneth Hernández Rodriguez  19 , Katiane Embiruçu Emilia  20 , Marcelo Andrés Kauffman  17 , Nury Isabel Mancilla  21 , Laureano Marcon  22 , Alessandra Marques Pereira  23 , Carolina Fischinger Moura de Souza  24 , Victor Adrián Muñoz  18 , Ricardo Andrés Naranjo Flórez  2 , André Luiz Pessoa  14 , María Victoria Ruiz  16 , Martha Luz Solano Villareal  25 , Norma Spécola  26 , Lina Marcela Tavera  27 , Javiera Tello  28   29 , Mónica Troncoso Schifferli  28   29 , Sonia Ugrina  30 , María Magdalena Vaccarezza  12 , Diane Vergara  28   29 , María Mercedes Villanueva  31
Affiliations

Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa

Norberto Guelbert et al. Mol Genet Metab Rep. .

Erratum in

Abstract

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa.

Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed.

Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values.

Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.

Keywords: Ataxia; Batten disease; CLN2; Cerliponase alfa; Enzyme replacement therapy; Epilepsy; Language delay; Pediatric.

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Conflict of interest statement

Dr. Atanacio has been a lecturer for the Biomarin Laboratory. Dr. Denzler has been a speaker for BioMarin. Dr. Durand has maintained a financial relationship with BioMarin through service contracts as speaker. Dr. Erlane has received travel grants, speaker fees, and educational grants from Biomarin. Dr. Espitia Segura reports a relationship with BioMarin Pharmaceutical Inc., including speaker fees and travel reimbursement. Dr. N Guelbert has received speaker fees from Biomarin. Dr. Pessoa has been a speaker for Biomarin. Dr. Naranjo and Dr. Tavera report a relationship with BioMarin Pharmaceutical Inc. that includes speaker and conference fees, as well as travel reimbursement.

Figures

Fig. 1
Fig. 1
Frequency of symptoms at the time of the first consultation in classic and typical patients.
Fig. 2
Fig. 2
Symptoms on follow-up of classic and atypical CLN2 patients.
See this image and copyright information in PMC

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