RESUMEN
BACKGROUND: Complement protein factor H (CFH) is a regulatory protein of the alternative complement pathway (AP); CFH mutations lead to a spectrum of different phenotypical manifestations of renal disease. CASE-DIAGNOSIS/TREATMENT: We report the case of a boy with a novel CFH gene mutation who presented with a membranoproliferative (MPGN) pattern of glomerular injury and developed 2 years later atypical hemolytic uremic syndrome (aHUS); this description shows that CFH alteration leads to two different renal diseases in the same patient. CONCLUSIONS: Our case suggests the possibility that complement dysregulation could determine different renal conditions, which may be part of the same disease spectrum. Early recognition of an evolution of glomerulopathies into aHUS may allow appropriate management and prevention of life-threatening consequences.
Asunto(s)
Glomerulonefritis Membranoproliferativa/genética , Síndrome Hemolítico-Urémico/genética , Enfermedades Renales/genética , Mutación , Adolescente , Síndrome Hemolítico Urémico Atípico , Biopsia , Factor H de Complemento/deficiencia , Factor H de Complemento/genética , Factor H de Complemento/inmunología , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/terapia , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/inmunología , Síndrome Hemolítico-Urémico/terapia , Enfermedades por Deficiencia de Complemento Hereditario , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Masculino , Fenotipo , Intercambio Plasmático , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin-producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases. RESULTS: In >70% of sporadic and familial cases, gene mutations, disease-associated factor H (CFH) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein (MCP) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH, C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations. CONCLUSIONS: Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant.