A carregar...
Publicação
Caso clínico : mutação no gene IBA57 como causa de leucodistrofia na idade pediátrica
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 631.53 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
A produção de ATP no corpo humano é dependente de um processo chamado fosforilação oxidativa. Este processo envolve vários complexos e a enzima ATP sintetase (complexo V). Os protões entram na matriz mitocondrial através do último complexo deste processo, a ATP sintetase, sendo necessários 3-4 protões para gerar uma molécula de ATP. Os clusters de Fe/S transportam os eletrões pela cadeia respiratória. Todo este processo é regulado pelo DNA mitocondrial e nuclear.
Mutações nos genes envolvidos na cadeia mitocondrial de transporte de eletrões e no processo da fosforilação oxidativa foram recentemente descritos como causa de leucodistrofias. Estas são doenças genéticas que afetam primariamente a substância branca.
Um dos genes envolvido é o gene IBA57 (1q42.13), que é responsável por codificar uma proteína localizada na mitocôndria e que faz parte do cluster Fe/S. A proteína em questão chama-se Putative Transferase CAF17 e está envolvida na maturação das proteínas mitocondriais 4Fe-4S. No caso de um defeito de maturação numa proteína mitocondrial especifica 4Fe-4S, várias doenças multissistémicas caraterizadas por encefalopatia, acidose lática e múltiplas disfunções mitocondriais têm sido reportadas. Estas doenças são raras, sendo poucos os casos descritos até à data.
Esta tese apresenta um caso clínico de uma criança com uma doença neurodegenerativa e um padrão imagiológico de leucodistrofia a quem foi detetado duas variantes em heterozigotia no gene IBA57 não descritas previamente na literatura nacional.
ATP production in the human body is a crucial metabolic process that depends on oxidative phosphorylation. This intricate process involves several complexes and the ATP synthase enzyme (complex V). The last complex in this process, ATP synthase, facilitates the entry of protons into the mitochondrial matrix. The generation of one molecule of ATP requires the participation of 3-4 protons. Fe/S clusters transport electrons through the respiratory chain, and the entire process is regulated by both mitochondrial and nuclear DNA. Recently, mutations in genes responsible for the mitochondrial electron transport chain and oxidative phosphorylation have been linked to leukodystrophies, genetic disorders that predominantly affect the white matter of the brain. One such gene implicated in this disease is the IBA57 gene (1q42.13), which encodes a mitochondrial Fe/S cluster protein known as Putative Transferase CAF17. This protein plays a vital role in the maturation of mitochondrial 4Fe-4S proteins. In cases where there is a defect in the maturation of a specific mitochondrial protein, 4Fe-4S, multisystemic diseases characterized by encephalopathy, lactic acidosis, and multiple mitochondrial dysfunctions have been reported. These diseases are rare, and few cases have been documented to date. The present thesis reports on a clinical case involving a child with a neurodegenerative condition and an imaging pattern indicative of leukodystrophy. Subsequent genetic analysis revealed the presence of two heterozygous variants in the IBA57 gene, unreported in national literature.
ATP production in the human body is a crucial metabolic process that depends on oxidative phosphorylation. This intricate process involves several complexes and the ATP synthase enzyme (complex V). The last complex in this process, ATP synthase, facilitates the entry of protons into the mitochondrial matrix. The generation of one molecule of ATP requires the participation of 3-4 protons. Fe/S clusters transport electrons through the respiratory chain, and the entire process is regulated by both mitochondrial and nuclear DNA. Recently, mutations in genes responsible for the mitochondrial electron transport chain and oxidative phosphorylation have been linked to leukodystrophies, genetic disorders that predominantly affect the white matter of the brain. One such gene implicated in this disease is the IBA57 gene (1q42.13), which encodes a mitochondrial Fe/S cluster protein known as Putative Transferase CAF17. This protein plays a vital role in the maturation of mitochondrial 4Fe-4S proteins. In cases where there is a defect in the maturation of a specific mitochondrial protein, 4Fe-4S, multisystemic diseases characterized by encephalopathy, lactic acidosis, and multiple mitochondrial dysfunctions have been reported. These diseases are rare, and few cases have been documented to date. The present thesis reports on a clinical case involving a child with a neurodegenerative condition and an imaging pattern indicative of leukodystrophy. Subsequent genetic analysis revealed the presence of two heterozygous variants in the IBA57 gene, unreported in national literature.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2023
Palavras-chave
Substância branca Leucodistrofia Gene IBA57 Fosforilação oxidativa Pediatria