BackgroundCow's milk is the most common food allergen in infants and the diagnosis of cow's milk allergy is difficult, even with the use of several diagnostic tests. Therefore, elimination diets and challenge tests are essential for the diagnosis and treatment of this disorder. The aim of this study is to report the clinical presentation and nutritional status of children evaluated by pediatric gastroenterologists for the assessment of symptoms suggestive of cow's milk allergy.MethodsAn observational cross-sectional study was performed among 9,478 patients evaluated by 30 pediatric gastroenterologists for 40 days in 5 different geographical regions in Brazil. Clinical data were collected from patients with symptoms suggestive of cow's milk allergy. The nutritional status of infants (age ≤ 24 months) seen for the first time was evaluated according to z-scores for weight-for-age, weight-for-height, and height-for-age. Epi-Info (CDC-NCHS, 2000) software was used to calculate z-scores.ResultsThe prevalence of suspected cow's milk allergy in the study population was 5.4% (513/9,478), and the incidence was 2.2% (211/9,478). Among 159 infants seen at first evaluation, 15.1% presented with a low weight-for-age z score (< -2.0 standard deviation - SD), 8.7% with a low weight-for-height z score (< -2.0 SD), and 23.9% with a low height-for-age z score (< -2.0 SD).ConclusionThe high prevalence of nutritional deficits among infants with symptoms suggestive of cow's milk allergy indicates that effective elimination diets should be prescribed to control allergy symptoms and to prevent or treat malnutrition.

Previous studies of human in vivo complement protein levels have only compared data for neonates with that from adult sera. Here, we establish the normal concentration ranges of the following complement regulatory proteins in healthy Brazilian children of different age groups (neonates: 1 month-1 year, 1-6 years and 6-13 years) and in adults: factor H (fH), factor I (fI), C4b-binding protein (C4 BP), properdin and vitronectin. We found that the concentrations of fH, fI, properdin and vitronectin in neonates are significantly lower than in adults. Remarkably, the concentration of C4 BP is below the method resolution (<50 micro g/ml) in 76% of the sera from neonates, while adults presented 199-532 microg/ml of C4 BP in their sera. The concentration of properdin in the sera from neonates and up to 1-year-old children was less than that observed in older children. Adults presented vitronectin levels significantly higher than all the other age groups in the study. No significant sex differences in the concentrations of all the studied regulatory proteins were detected. This study reveals the ontogeny of complement system in greater detail than previously available and may point to the reasons why neonates have higher susceptibility to develop life-threatening pyogenic infections. These reference values will be of use in clinical and laboratory investigations of disorders associated with low levels of these regulatory proteins.

Here we describe two new cases of complete deficiency of factor I (fI) in two sisters from a consanguineous Brazilian family. The eldest sibling (20-year-old) developed systemic lupus erythematosus (SLE) early during childhood while the youngest had been committed on several occasions owing to repeated infections although she was asymptomatic for auto-immune diseases. We also detected lower concentrations of C3 and factor B in both sisters. Biological functions dependent on complement activation such as the production of opsonins and killing of phagocytozed micro-organisms, chemotactic factors and haemolytic activity were all significantly reduced in both probands. Consistent with the absence of fI and low levels of fH, a deregulated production of C3b was observed by bidimensional electrophoresis in sera of both the probands.

There is a lack of medical awareness concerning PIDs, even among paediatricians, who have been targeted with PID educational programmes in recent years in Brazil. An increase in awareness with regard to these disorders within the medical community is an important step towards improving recognition and treatment of PIDs.

SUMMARYWe have studied the molecular basis of factor I (fI) deficiency in two Brazilian sisters from a consanguineous family. By reverse transcription-polymerase chain reaction we observed that all fI cDNA amplified products from one sister had the same size as those of normal cDNA, however, they were significantly less intense. Sequencing analysis of subcloned cDNA revealed a dinucleotide insertion (AT) between positions 1204 and 1205 in the 11th exon that creates a stop codon 13 bp downstream of the insertion site. Genomic DNA sequencing and heteroduplex analysis confirmed that both probands are homozygous for this mutation, whereas their parents are heterozygous. The stop codon and the diminished amounts of fI cDNA could indicate increased fI mRNA instability, perhaps due to a mechanism of nonsense-mediated decay. This hypothesis is consistent with our observation that treatment with the translation inhibitor cycloheximide stabilized fI mRNA expression in proband's fibroblasts.