D-bifunctional protein deficiency – a cause of neonatal onset seizures and hypotonia

• Autor(a) principal: Nascimento, J.
• Data de Publicação: 2015
• Outros Autores: Mota, C., Lacerda, L., Pacheco, S., Chorão, R., Martins, E., Garrido, C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/1744
• topic: D-bifunctional protein deficiency; neonatal seizures; peroxisome; polymicrogyria

Background Peroxisomal disorders are classified in two major groups: (1) Peroxisome Biogenesis Disorders and (2) single Peroxisomal Enzyme/Transporter Deficiencies. D-bifunctional protein deficiency (DBP; OMIM #261515) included in this last group of rare diseases leads to an impaired peroxisomal beta-oxidation. D-bifunctional protein deficiencies are classified in four types based on the degree of activity of the 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase protein units. Case report/Result The authors present the first portuguese reported type II DBP deficiency patient, whose neonatal clinical picture is indistinguishable from a Zellweger spectrum disease. The clinical features and the neuroimaging findings of polymicrogyria raised suspicion of the diagnosis. After biochemical analysis, DBP deficiency was confirmed with the identification of p.Asn457Tyr (N457Y) mutation, present in homozygosity in HSD17B4 gene. Parents were found to be carriers of the mutated allele, confirming the patient homozygosity status and allowing prenatal diagnosis to future pregnancies. Conclusion D-bifunctional protein deficiency is a rare and severe disease and final diagnosis can only be accomplished after HSD17B4 gene sequencing. Treatment is generally of supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting the eventual progression of liver disease.