Dados do Trabalho

Título

CEROID NEURONAL LIPOFUSCINOSIS TYPE 3: PHENOTYPE VARIABILITY IN DIZYGOTIC TWINS

Apresentação dos casos

We report two thirteen years old dyzigotic twin girls with a biallelic pathogenic variant in CLN3 gene. Patient one presented vision loss associated with macular dystrophy, complex pattern seizures at age nine, and evolved to progressive ataxia at eleven years old. Patient two presented with vision loss and progressive ataxia at the age of eleven without history of seizures. Pregnancy history was marked by maternal hypertension and urinary infection at seventh month and was treated with methyldopa and cephalexin respectively, steroids were taken by the mother for pulmonary maturation, no other intercurrences were referred. They are daughters of a consanguineous couple with no similar cases in their family. They were born thirty-six weeks with no intercurrences. At physical examination both presented ataxic gait and dysdiadochokinesia. The patient 1 is blind, and patient 2 has low vision. A retinopathy custom NGS panel evidenced a biallelic pathogenic variant in CLN3 gene [c.1000G>A / p. (Arg334Cys)] confirming the diagnosis of ceroid neuronal lipofuscinosis type 3.

Discussão

Ceroid neuronal lipofuscinosis type 3 is a characteristic juvenile form of ceroid neuronal lipofuscinosis with vision loss and macular degeneration, a hallmark of the disease. Progressive cognitive impairment, behavioral alterations, motor symptoms and epilepsy can be present during disease development. It is inherited as an autosomal recessive pattern with mutations in CNL3 which codes battenin, an important protein in the lipid metabolism and late stage endosomal and vesicle trafficking affecting many cellular processes.

Comentários finais

This report evidences the importance of age onset and vision loss for the suspicion of ceroid neuronal lipofuscinosis type 3, and clinical progression differentiation of other types of lipofuscinosis. It also evidence phenotype variability of disease even among members of the same family with the same genetic alteration.

Referências

1.Aungaroon G, Hallinan B, Jain P, Horn PS, Spaeth C, Arya R. Correlation Among Genotype, Phenotype, and Histology in Neuronal Ceroid Lipofuscinoses: An Individual Patient Data Meta-Analysis. Pediatr Neurol. 2016 Jul;60:42-48.e4. doi: 10.1016/j.pediatrneurol.2016.03.018. Epub 2016 Apr 8. PMID: 27238410.

2.Bennett MJ, Rakheja D. The neuronal ceroid-lipofuscinoses. Dev Disabil Res Rev. 2013;17(3):254-9. doi: 10.1002/ddrr.1118. PMID: 23798013.

3. Simonati A, Williams RE. Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview. Front Neurol. 2022 Mar 11;13:811686. doi: 10.3389/fneur.2022.811686. PMID: 35359645; PMCID: PMC8961688.

Palavras Chave

Lipofuscinose Ceróide tipo 3; Neurogenética; Erros Inatos do Metabolismo