Dados do Trabalho

Título

CLINICAL AND MOLECULAR PROFILE OF INFANTILE NEUROAXONAL DYSTROPHY (INAD) IN BRAZILIAN PATIENTS: A CASE STUDY SERIES

Introdução

Infantile Neuroaxonal Dystrophy (INAD) is an ultra-rare and devastating neurodegenerative disorder, classified as a major subtype of PLA2G6-associated neurodegeneration (PLAN).
INAD typically manifests between 6 months and 3 years of age, marked by psychomotor regression, gait disturbances, and progressive spastic tetraparesis. Disease progression is rapid, with severe cognitive decline, optic atrophy, and bulbar dysfunction leading to early mortality, usually before the second decade of life. Seizures may occur in a minority of cases, either early or late in the disease trajectory.
Our study endeavors to shed light on the clinical and molecular profile of INAD among Brazilian patients. This research aims to contribute to the broader comprehension of INAD and potentially guide future research endeavors and therapeutic interventions aimed at enhancing patient outcomes.

Objetivo

This study aims to elucidate the clinical and molecular characteristics of Infantile Neuroaxonal Dystrophy (INAD) among Brazilian patients, a subtype of PLA2G6-associated neurodegeneration (PLAN), characterized by progressive motor and cognitive decline leading to significant morbidity and premature mortality.

Método

We conducted a retrospective cross-sectional study, analyzing data collected through structured questionnaires administered via interviews with patients or their caregivers. The study encompassed clinical, radiographic, laboratory, and neurophysiologic features of 21 patients diagnosed with INAD in Brazil from August 2023 to February 2024.

Resultados

The findings reveal a spectrum of clinical presentations among the INAD patients, including psychomotor regression and spastic tetraparesis. Radiographic and neurophysiological assessments highlighted involvement of specific brain regions, particularly the cerebellum and basal ganglia. A significant discovery was the identification of a high incidence of PLA2G6 mutations, including several novel variants.

Conclusão

The study offers valuable insights into the clinical and molecular profiles of INAD within the Brazilian population, addressing the paucity of data for this group. These insights enhance the understanding of the natural history of INAD, aiding in the development of improved clinical management strategies and identifying potential therapeutic targets. Furthermore, this research contributes to the global understanding of the disease by expanding the phenotypic description of INAD.

Referências

Altuame, F.D., Foskett, G., Atwal, P.S. et al. The natural history of infantile neuroaxonal dystrophy. Orphanet J Rare Dis 15, 109 (2020). https://doi.org/10.1186/s13023-020-01355-2

Gregory A, Westaway S, Holm IE, Kotzbauer P, Hogarth P, Sonek S, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology. 2008;71(18):1402–1409.

Kurian M, Morgan N, MacPherson L, Foster K, Peake D, Gupta R, et al. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology. 2008;70(18):1623–9.

Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ. PLA2G6-associated neurodegeneration. GeneReviews®. Seattle: University of Washington; 2017.

Carrilho I, Santos M, Guimarães A, Teixeira J, Chorão R, Martins M, et al. Infantile neuroaxonal dystrophy: what's most important for the diagnosis? Eur J Paediatr Neurol. 2008;12(6):491–500.

Wu Y, Jiang Y, Gao Z, Wang J, Yuan Y, Xiong H, et al. Clinical study and PLA2G6 mutation screening analysis in Chinese patients with infantile neuroaxonal dystrophy. Eur J Neurol. 2009;16(2):240–5

Palavras Chave

Infantile neuroaxonal dystrophy; PLA2G6-associated neurodegeneration; Neurodegenerative disorders