RESUMEN
Niemann-Pick diseases are hereditary neurovisceral lysosomal lipid storage disorders, of which the rare type C2 almost uniformly presents with respiratory distress in early infancy. In the patient presented here, the NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa. Protein expression was strongly reduced also in alveolar macrophages. The infant developed failure to thrive and tachypnea. Lung lavage, computer tomography, and histology showed typical signs of pulmonary alveolar proteinosis with an abnormal intraalveolar accumulation of surfactant as well as macrophages. An NPC2-hypomorph animal model also showed pulmonary alveolar proteinosis and accumulation of macrophages in the lung, liver, and spleen long before the mice died. Due to the elevation of cholesterol, the surfactant had an abnormal composition and function. Despite the removal of large amounts of surfactant from the lungs by therapeutic lung lavages, this treatment was only temporarily successful and the infant died of respiratory failure. Our data indicate that respiratory distress in NPC2 disease is associated with a loss of normal NPC2 protein expression in alveolar macrophages and the accumulation of functionally inactive surfactant rich in cholesterol.
Asunto(s)
Enfermedad de Niemann-Pick Tipo C/complicaciones , Proteinosis Alveolar Pulmonar/complicaciones , Enfermedades Respiratorias/etiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/sangre , Proteínas Portadoras/química , Proteínas Portadoras/genética , Femenino , Mutación del Sistema de Lectura , Glicoproteínas/sangre , Glicoproteínas/química , Glicoproteínas/genética , Humanos , Lactante , Ratones , Datos de Secuencia Molecular , Enfermedad de Niemann-Pick Tipo C/diagnóstico por imagen , Enfermedad de Niemann-Pick Tipo C/patología , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/patología , Radiografía , Enfermedades Respiratorias/complicaciones , Enfermedades Respiratorias/diagnóstico por imagen , Enfermedades Respiratorias/patología , Proteínas de Transporte VesicularRESUMEN
BACKGROUND: the purpose of this study was to investigate the presence of respiratory allergy in 30 Mexican patients bearing cystic fibrosis (CF). METHODS AND RESULTS: all patients completed a clinical history, had a physical examination, total serum IgE, nasal and blood eosinophils determinations and evaluation of skin prick tests for 36 allergens. In 26.6% of the patients included in the study was detected respiratory allergy diagnosed on clinical and laboratory analyses. Skin prick tests of 11 (36.6%) of the patients were positive to at least one allergen and Aspergillus fumigatus (A. fumigatus) was the most frequently observed allergen in 23% of the cases. CONCLUSIONS: we have demonstrated in this study that Mexican patients also present a coexistence of respiratory allergy in patients bearing CF.