Asunto(s)
Encéfalo/patología , Trastorno Peroxisomal/enzimología , Racemasas y Epimerasas/deficiencia , Temblor/etiología , Terapia Combinada , Trastorno Depresivo/complicaciones , Disartria/enzimología , Disartria/genética , Electroencefalografía , Ácidos Grasos/administración & dosificación , Ácidos Grasos/sangre , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Paresia/etiología , Trastorno Peroxisomal/dietoterapia , Trastorno Peroxisomal/genética , Trastorno Peroxisomal/patología , Trastorno Peroxisomal/terapia , Ácido Fitánico/administración & dosificación , Intercambio Plasmático , Racemasas y Epimerasas/genética , Reflejo Anormal , Retinitis Pigmentosa/enzimología , Retinitis Pigmentosa/genética , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: To determine the enzymatic defect in a patient with ataxia, dysarthric speech, dry skin, hypotonia, and absent reflexes. The patient was previously diagnosed with a presumed deficiency of trihydroxycholestanoyl-CoA oxidase. BACKGROUND: Peroxisomes harbor a variety of metabolic functions, including fatty acid beta-oxidation, etherphospholipid biosynthesis, phytanic acid alpha-oxidation, and L-pipecolic acid oxidation. This patient was previously described with an isolated peroxisomal beta-oxidation defect caused by a deficiency of the enzyme trihydroxycholestanoyl-CoA oxidase. This was based on the pattern of accumulating metabolites. METHODS: Measurement of beta-oxidation enzymes, peroxisomal biochemical analysis in body fluids and cultured skin fibroblasts, and DNA analysis of the PEX12 gene were performed. RESULTS: An isolated beta-oxidation defect in this patient was excluded by measurement of the various beta-oxidation enzymes. The authors found that the patient had a peroxisome biogenesis disorder caused by mutations in the PEX12 gene, although all peroxisomal functions in cultured skin fibroblasts were normal. CONCLUSIONS: The absence of clear peroxisomal abnormalities in the patient's fibroblasts, including a normal peroxisomal localization of catalase, implies that even when all peroxisomal functions in fibroblasts are normal, a peroxisome biogenesis disorder cannot be fully excluded, and further studies may be needed. In addition, the authors' findings imply that there is no longer evidence for the existence of trihydroxycholestanoyl-CoA oxidase deficiency as a distinct disease entity.