Cystic Fibrosis Newborn Screening in Portugal: PAP Value in Populations with Stringent Rules for Genetic Studies.

Newborn screening (NBS) for cystic fibrosis (CF) has been shown to be advantageous for children with CF, and has thus been included in most NBS programs using various algorithms. With this study, we intend to establish the most appropriate algorithm for CF-NBS in the Portuguese population, to determine the incidence, and to contribute to elucidating the genetic epidemiology of CF in Portugal. This was a nationwide three-year pilot study including 255,000 newborns (NB) that were also screened for congenital hypothyroidism (CH) and 24 other metabolic disorders included in the Portuguese screening program. Most samples were collected in local health centers spread all over the country, between the 3rd and 6th days of life. The algorithm tested includes immunoreactive trypsinogen (IRT) determination, pancreatitis associated protein (PAP) as a second tier, and genetic study for cases referred to specialized clinical centers. Thirty-four CF cases were confirmed positive, thus indicating an incidence of 1:7500 NB. The p.F508del mutation was found in 79% of the alleles. According to the results presented here, CF-NBS is recommended to be included in the Portuguese NBS panel with a small adjustment regarding the PAP cut-off, which we expect to contribute to the improvement of the CF-NBS performance. According to our results, this algorithm is a valuable alternative for CF-NBS in populations with stringent rules for genetic studies.

Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

Pos-infectious bronchiolitis obliterans in children.

Bronchiolitis obliterans (BO) is a rare disease in immunocompetent children that usually occurs after infection of the lower airways. While a diagnosis of BO was usually confirmed by lung biopsy, identification of prior lung lesion plus a typical clinical course and a suggestive chest X-ray and CT scan have replaced the need for more invasive procedures. The authors reviewed the clinical records of 10 BO patients, followed in the Outpatients Paediatric Pulmonology Unit from January 1997 to December 2002, to identify the most common aetiology, clinical and radiological profiles, treatment and course. All patients maintained cough and/or wheezing after the initial acute episode. 80% had failure to thrive at the time of the diagnosis, mean age 16 months. Viral pneumonia was the main initial event (5 adenovirus, 3 respiratory syncytial virus, 1 parainfluenza virus, 1 unknown). Lung biopsies were not performed as clinical and radiological presentations were typical of BO. The follow-up (mean 36 months) revealed clinical resolution in 3 children and persistent symptoms in 6. One patient had progressive respiratory failure and died. Prompt recognition of the diagnosis with supportive treatment that included oxygen therapy and an aggressive nutrition plan helped to improve the clinical state of the children.

Cystic Fibrosis--clinical features of a sample of Portuguese patients.

Even though there have been rapid advances in the comprehension of molecular determinants of Cystic Fibrosis, this disease continues to be one of the most common lethal recessive diseases in the Caucasian population worldwide. The reality of Portuguese patients is still greatly unknown, due to the lack of studies published in reference to our population. The objectives of this study were: clinical evaluation of a group of Portuguese patients with Cystic Fibrosis, with two identified mutations; comparing the clinical presentation of a group of homozygous patients for the F508del mutation with patients that are not homozygous for this mutation. A group of patients, followed in Pediatric Pneumology Consultations of S. João Hospital, were characterised in terms of phenotype and were classified according to criteria of severity. All of the patients in this group presented class I and/or II mutations, classically associated with a more severe phenotype. In conformity with the severe genotype, all patients presented a phenotype of pancreatic insufficiency but with greater variability of pulmonary manifestations. Significant variations were not found in terms of age at diagnosis, presenting forms and disease severity between F508del homozygous patients and the other patients. On the other hand, patients with the same genotype (homozygous F508del) presented different spectrums of clinical manifestations and phenotype severity. Just as much, or even more than the genotype characterisation, the time period of evolution of the disease and external factors, namely being subjected to infectious stimulus, interfere in the severity of the phenotype, at a certain moment in time.