Luísa Lobo

A Novel Mutation of the HNF1B Gene Associated With Hypoplastic Glomerulocystic Kidney Disease and Neonatal Renal Failure: A Case Report and Mutation Update

AbstractHepatocyte nuclear factor 1 beta (HNF1B) plays an important role in embryonic development, namely in the kidney, pancreas, liver, genital tract, and gut. Heterozygous germline mutations of HNF1B are associated with the renal cysts and diabetes syndrome (RCAD). Affected individuals may present a variety of renal developmental abnormalities and/or maturity-onset diabetes of the young (MODY).A Portuguese 19-month-old male infant was evaluated due to hypoplastic glomerulocystic kidney disease and renal dysfunction diagnosed in the neonatal period that progressed to stage 5 chronic renal disease during the first year of life. His mother was diagnosed with a solitary hypoplastic microcystic left kidney at age 20, with stage 2 chronic renal disease established at age 35, and presented bicornuate uterus, pancreatic atrophy, and gestational diabetes. DNA sequence analysis of HNF1B revealed a novel germline frameshift insertion (c.110_111insC or c.110dupC) in both the child and the mother. A review of the literature revealed a total of 106 different HNF1B mutations, in 236 mutation-positive families, comprising gross deletions (34%), missense mutations (31%), frameshift deletions or insertions (15%), nonsense mutations (11%), and splice-site mutations (8%).The study of this family with an unusual presentation of hypoplastic glomerulocystic kidney disease with neonatal renal dysfunction identified a previously unreported mutation of the HNF1B gene, thereby expanding the spectrum of known mutations associated with renal developmental disorders.

Clinical, Radiological, and Physiological Differences Between Obliterative Bronchiolitis and Problematic Severe Asthma in Adolescents and Young Adults: The Early Origins of the Overlap Syndrome?

Few reports have compared chronic obstructive lung diseases (OLDs) starting in childhood.

Vitamin D-dependent rickets: a resurgence of the rachitic lung in the 21st century.

Respiratory complications of rickets may be life-threatening particularly in developing countries. A 7-month-old boy presented with recurrent infections, seizures, failure to thrive, wheezing and respiratory distress progressing to global respiratory failure. Several antimicrobial regimens, bronchodilators and corticosteroids resulted in only short-term improvement. He was transferred from Cape Verde to a third-care hospital in Portugal. He was hypotonic and undernourished, with respiratory anguish and classical skeletal signs of rickets, despite vitamin D supplementation. Hypocalcaemia, normal phosphate levels and normal vitamin D status 25(OH)D3 and 1.25(OH)2D3) pointed to vitamin D-dependent rickets type II. Treatment with high doses of calcium and calcitriol allowed progressive respiratory, musculoskeletal and neurological recovery. Although respiratory manifestations of rickets were described many years ago, the present case raises relevant issues about the level of diagnostic support, the risk of complications and how they should be assessed and monitored.

Double aortic arch as cause of persistent stridor: sequential imaging for preoperative assessment.

a Serviço de Pediatria, Hospital Garcia de Orta, Almada, Portugal b Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal c Serviço de Pediatria, Centro Hospitalar de Leiria, Leiria, Portugal d Serviço de Cardiologia Pediátrica, Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal e Serviço de Radiologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal f Unidade de Pneumologia Pediátrica, Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal

Duplo arco aórtico na origem de estridor persistente: sequência de imagens para orientação cirúrgica

a Serviço de Pediatria, Hospital Garcia de Orta, Almada, Portugal b Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal c Serviço de Pediatria, Centro Hospitalar de Leiria, Leiria, Portugal d Serviço de Cardiologia Pediátrica, Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Carnaxide, Portugal e Serviço de Radiologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal f Unidade de Pneumologia Pediátrica, Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisboa, Portugal

Discinesia ciliar primária revisitada: A propósito de três casos clínicos

Primary ciliary dyskinesia is a genetically and clinically heterogeneous disorder. Its pathogenesis reflects structural and functional compromise of the cilia. Common clinical manifestations include recurrent upper and lower respiratory tract infections and infertility, as well as situs inversus totalis in half of the affected patients. Besides its rarity and phenotypic heterogeneity its diagnosis usually requires a high suspicion index. The main purpose of this paper is to review the pathogenesis, clinical features, diagnostic and therapeutic approaches of primary ciliary dyskinesia beyond the discussion of three clinical reports. We report the cases of three patients all with a past history of neonatal respiratory distress and two with situs inversus totalis. The subsequent clinical manifestations included lower airway symptoms in two patients (chronic productive cough and recurrent pneumonia and wheezing) and upper respiratory tract disease in all patients. Age at primary ciliary dyskinesia diagnosis differed considerably among patients (8 months, 5 and 12 years). The two patients with later diagnosis had already obstructive lung function compromise at the time of diagnosis. The authors discuss the different clinical patterns presented, therapeutic strategies and the clinical progression that ensued, factors possibly implicated in late diagnosis and its prognostic consequences. The main goal is to emphasize early and/or prevalent clinical features of primary ciliary dyskinesia in order to promote clinical awareness and early recognition of the disease.Resumo A discinesia ciliar primaria e uma doenca genetica e clinicamente heterogenea, cuja patogenese assenta em compromisso da estrutura e funcao ciliares. Cursa habitualmente com infeccoes respiratorias recorrentes, infertilidade e ainda situs inversus total em cerca de metade dos doentes. Dada a raridade e heterogeneidade fenotipica desta patologia o seu diagnostico implica frequentemente um elevado indice de suspeicao. Com este artigo os autores procuraram rever os aspectos fundamentais relativos a etiopatogenese, quadro clinico e abordagens diagnostica e terapeutica da discinesia ciliar primaria, contextualizando-os na discussao de tres casos clinicos. Descrevem-se tres doentes cujo quadro clinico inaugural foi marcado por sindroma de dificuldade respiratoria neonatal associada, em dois doentes, a situs inversus total. A evolucao clinica subsequente cursou com sintomatologia respiratoria em dois doentes (tosse produtiva cronica num doente e episodios recorrentes de pneumonia e sibilância noutro) e atingimento do aparelho respiratorio superior nos tres. A data do diagnostico de discinesia ciliar primaria, os doentes apresentavam idades distintas (8 meses, 5 e 12 anos), sendo que os dois doentes com idades de diagnostico mais tardias apresentavam nessa altura compromisso funcional respiratorio do tipo obstrutivo. Os autores discutem os diferentes padroes de apresentacao clinica, a abordagem terapeutica e a evolucao clinica subsequente, os factores potencialmente implicados no diagnostico tardio e as suas repercussoes prognosticas. O objectivo primordial e alertar para manifestacoes clinicas precoces e/ou frequentes de discinesia ciliar primaria, procurando deste modo influenciar o prognostico pela melhoria do reconhecimento precoce desta patologia.