Dados do Trabalho

Título

DEFECT IN 14B PEROXISOMAL BIOGENESIS EVIDENCING CLINICAL MANIFESTATIONS BY MUTATION IN THE PEX11B GENE

Apresentação do caso

MRGS, male, 23 years old. At 3 months old presented nystagmus episodes and congenital cataract was evidenced. Evolved with generalized tonic-clonic seizures, neuropsychomotor development delay and hyporeflexia in the lower limbs. Exome evidenced defect in 14B peroxisomal biogenesis (PBD14B) (OMIM # 614920), which may lead to loss of function of the main PEX11B gene transcript. Genetic counseling was recommended. Currently using anti-seizure polypharmacy, still presents seizures, walking difficulties, dyspraxia and dysarthria, and symptoms of severe autism.

Discussão

The peroxisome plays pivotal roles in the plasmalogen, cholesterol and biliar acids synthesis, and in the very-long-chain fatty acids catabolization. Its biogenesis involves different processes in which peroxins or PEX proteins are involved and are encoded by PEX genes. Peroxisomal disorders constitute the inborn errors of metabolism and are still few reported due to the fact that they are quite rare and to the short-time existence of the exome, the test that identifies the genetic alterations. Defects in peroxisomal biogenesis caused by biallelic mutations in the peroxin genes (PEX) generate accumulation of fatty acids in the body, which are harmful to neuronal cells. In the described case, the exome revealed a defect in 14B peroxisomal biogenesis (PBD14B), an autosomal recessive disorder. It is caused by mutation in the PEX11B gene on chromosome 1q21 and is characterized by mild intellectual disability, congenital cataract, progressive hearing loss and polyneuropathy. They may be associated with dysmorphisms, malformations, neurological regression, hypotonia, seizures, cataracts, retinopathy, hepatomegaly and jaundice.

Comentários finais

Regardless the fact that inborn errors of metabolism are incurable, recent advances in medicine have significant raised improvement for the quality of life of those affected ones, guaranteeing them a greater chance of survival, while new more effective and definite treatments are developed. To date, only a limited number of peroxisomal biosynthesis’ disorders caused by PEX11B gene mutations have been clinically discovered. Therefore, expanding neonatal screening programs is crucial for early diagnosis, which, in turn, leads to interventions in the first year of life, which enables a better prognosis and the development of new management strategies for the disease in the future.

Referências (se houver)

Palavras Chave

Peroxisomal disorder, exome, lipid metabolism, inborn errors.

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

The authors declare that they have no conflict of interests or benefits in any form related to the subject of this report.

Área

Erros inatos do metabolismo