RESUMO
Abstract Objectives: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel. Methods: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out. Results: Twenty-three PwCF (12 male), with a median age of 12 years, were followed up. All patients carry the F508del mutation in at least one allele. Fifteen PwCF were F508del-homozygous, median BMI z-score was -0.13, all are pancreatic insufficient and median FEV1 value was 78.1%. These PwCF are eligible for dual therapy (lumacaftor/tezacaftor+ivacaftor) and for triple therapy (tezacaftor+ivacaftor+elexacaftor). PwCF with 711 +1G->T (n = 2), 2184insA (n = 1) mutations and a novel mutation c.3321dup (n = 1) have minimal function mutation and patients with a residual function mutation: R334W (n = 3) and P5L (n = 1) have a less severe phenotype. All these patients, because they also carry F508del mutation, are elegible to triple therapy. Conclusions: Genetic and molecular characterization of PwCF poses an important step not just for CF diagnosis and prognosis which is tightly correlated with the clinical phenotype, but also for the eligibility of CFTR modulator drugs.
RESUMO
ABSTRACT Idiopathic pulmonary hemosiderosis is a potentially fatal disease that results from episodes of alveolar hemorrhage of unknown origin. The clinical spectrum is varied, and anemia may constitute the only manifestation of illness, preceding other signs and symptoms by several months. We present the case of a 4 year-old child presenting with fever, vomiting and prostration, associated with pallor. He had microcytic and hypochromic anemia refractory to iron therapy. Gastrointestinal bleeding was ruled out after negative extensive etiological investigation. Subsequently, pulmonary infiltrates suggestive of alveolar hemorrhage were observed in the chest radiography. The cytological exam of the bronchoalveolar lavage showed hemosiderin-laden macrophages. After the etiological study, the diagnosis of idiopathic pulmonary hemosiderosis was made by exclusion. He was initiated on corticosteroid therapy, later associated to an immunosuppressive agent, with subsequent correction of anemia and of the radiological pattern. The patient is currently asymptomatic.
RESUMO A hemossiderose pulmonar idiopática é uma doença potencialmente fatal que cursa com episódios de hemorragia alveolar de etiologia desconhecida. As manifestações clínicas são variadas, e a anemia pode constituir o único sinal de doença, precedendo em vários meses os outros sinais e sintomas. Apresenta-se o caso de criança de 4 anos, com febre, vômitos e prostração, associados à palidez. Apresentava anemia microcítica e hipocrômica, refratária à terapêutica com ferro. A hipótese diagnóstica de sangramento gastrintestinal foi excluída, após investigação etiológica extensa, inconclusiva. Posteriormente, em radiografia torácica, foram observados infiltrados sugestivos de hemorragia alveolar. O exame citológico do lavado broncoalveolar mostrou macrófagos com depósitos de hemossiderina. Após estudo etiológico, assumiu-se, por exclusão, o diagnóstico de hemossiderose pulmonar idiopática. Foi iniciada terapêutica com corticoides, associada posteriormente a imunossupressor, com correção subsequente da anemia e do padrão radiológico, encontrando-se, atualmente, assintomático.