Défice do Cofactor Molibdénio. Um Diagnóstico Diferencial no Recém-Nascido com Convulsões

Descrevemos um lactente com doença neurológica grave caracterizada por convulsões mioclónicas e tónicas, com início no período neonatal, refractárias a vários anticonvulsivantes, assim como, tetraparésia espástica. A tomografia computorizada e a ressonância magnética cerebrais evidenciaram imagens de leucomalácia periventricular e, posteriormente, de atrofia cerebral progressiva e encefalomalácia quística. Os exames bioquímicos e o estudo da actividade enzimática permitiram o diagnóstico de défice do cofactor molibdénio. O défice do cofactor molibdénio é uma doença rara, autossómica recessiva, que se comporta como um défice combinado da sulfito oxidase e da xantina desidrogenase (ou xantina oxidase) alterando o metabolismo das purinas e da cisteína. A terapêutica é controversa e o prognóstico reservado. O nosso objectivo é relembrar esta patologia no diagnóstico diferencial das convulsões neonatais e da encefalopatia hipóxico- -isquémica, sobretudo quando os exames imagiológicos sugerem lesões de leucomalácia no recém-nascido de termo. Salientamos a importância deste diagnóstico diferencial, apesar do prognóstico pobre, devido à possibilidade de aconselhamento genético adequado e diagnóstico pré-natal.

Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA