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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(03): 284-295
DOI: 10.1055/s-0043-1761434
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Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group

Manejo clínico e diagnóstico da doença CLN2: consenso do grupo de especialistas brasileiros
Leticia Pereira de Brito Sampaio 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
,
Maria Luiza Giraldes de Manreza 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
,
André Pessoa 
2   Universidade Estadual do Ceará, Hospital Infantil Albert Sabin, Fortaleza CE, Brazil.
,
Juliana Gurgel-Giannetti 
3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Hospital das Clínicas, Belo Horizonte MG, Brazil.
,
Ana Carolina Coan 
4   Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas SP, Brazil.
,
Hélio van der Linden Júnior 
5   Instituto de Neurologia de Goiânia, Goiânia GO, Brazil.
,
Emília Katiane Embiruçu 
6   Universidade do Estado da Bahia, Hospital Universitário Professor Edgard Santos, Salvador BA, Brazil.
,
Adélia Maria de Miranda Henriques-Souza 
7   Instituto de Medicina Integral Professor Fernando Figueira, Recife PE, Brazil.
,
Fernando Kok 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
› Author Affiliations Support BioMarin Brasil Farmaceutica LTDA provided financial support for the medical writer assistance. The funder played no role in the content of this publication.
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Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

Resumo

Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes.

Keywords

Neuronal Ceroid-Lipofuscinoses - Language Development Disorders - Consensus - Enzyme Replacement Therapy - Epilepsy

Palavras-chave

Lipofuscinoses Ceroides Neuronais - Transtornos do Desenvolvimento da Linguagem - Consenso - Terapia de Reposição Enzimática - Epilepsia

Authors' Contributions

All authors performed the literature research, prepared the questions, voted, and discussed the topics. They reviewed all drafts of the present manuscript and approved the final version.


Supplementary Material



Publication History

Received: 04 October 2021

Accepted: 15 March 2022

Article published online:
14 April 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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