Novel mutation in the epithelial sodium channel causing type I pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis.

UNLABELLED: Cystic fibrosis (CF) is an inherited disorder with a devastating prognosis. Determination of chloride concentration in sweat has been the gold standard test for diagnosing CF for over 50 years and still remains the primary screening test. However, now that the genetic cause is known and can be studied, genetic confirmation is mandatory in every suspected patient. We present a patient who had been clinically diagnosed and whose genetic testing could not confirm CF, leading us to search for other options that may also give a positive sweat test. The patient turned out to suffer type 1 pseudohypoaldosteronism, a condition that may cause severe dehydration, hyponatremia and hyperkalemia episodes if not diagnosed and treated early with sodium supplementation. We found a genetic variation in the epithelial sodium channel gene which has not been reported previously, and we discuss the possibility of it being the cause of our patient's phenotype. CONCLUSION: this patient clearly illustrates the usefulness of genetic confirmation for CF for the diagnosis and genetic counselling, even when it is clinically oriented, and describes a novel mutation of the amiloride-sensitive epithelial sodium channel possibly causing type 1 pseudohypoaldosteronism.

Predicting the growth response of children with idiopathic growth hormone deficiency to one year of recombinant growth hormone treatment: derivation and validation of a useful method.

Patients with idiopathic growth hormone (GH) deficiency (iGHD) show a wide interindividual variability in their response to recombinant GH (rGH) therapy. Accurate growth prediction would provide clinicians a helpful tool for planning and optimizing growth promoting therapy. We develop and validate a model to predict the growth response, using accessible parameters and simple calculations. Data of 132 prepubertal patients with iGHD, receiving rGH treatment for at least one year, were collected. The sample was split into two statistically similar groups: a derivation set (100 children) and a validation set (32 children). Linear multiple regression, stepwise analysis, was used to derive the model. Validation was performed by calculating the difference in predictive power when applying it to the validation group ('shrinkage'), and analyzing the differences between the predicted and observed responses ('studentized residual'). The obtained prediction model predicts 97.8% of the variability of height achieved after one year of therapy (error SD = 1.767 cm). All data integrated in our model are accessible to the clinician when evaluating the patient and the calculations are fast and simple. It is an accurate method that fulfills all the requirements for becoming a useful tool to predict growth response in prepubertal children with iGHD and should be helpful optimizing rGH therapy.

[GHBP, IGF-1 and IGFBP-3 serum levels in familial short-statured and normal-statured children]. / Concentración sérica de GHBP, IGF-1 e IGFBP-3 en niños con talla baja familiar y con talla normal.

BACKGROUND AND OBJECTIVE: Growth hormone binding protein (GHBP), insuline-like growth factor 1 (IGF-1) and insuline-like growth factor binding protein 3 (IGFBP-3) serum concentrations were studied in familial short-statured patients (FSS) and age-matched normal-statured subjects. The aim of the study was to ascertain whether differences in growth factors concentrations between groups could be shown and whether they may contribute to explaining the different patterns of growth in both groups. SUBJECTS AND METHOD: Serum samples of 38 FSS patients (20 boys) and 31 normal-statured subjects (15 boys) in Tanner I stage (prepubertal), were analysed in a central laboratory. All auxological parameters (height, growth velocity, target height, body mass index (BMI) and biochemical parameters (IGF-1 and IGFBP-3) were standardised for age and sex-matched subjects. GHBP values were expressed as percentage of specific binding. RESULTS: The studied populations were similar and no statistically-significant differences in chronological age, bone age and BMI were found. Height, growth velocity and target height were significantly lower in FSS patients compared with normal subjects (p < 0.0001). IGF-1, IGFBP-3 and GHBP concentrations were significantly lower in the FSS group (p < 0.01). Correlations were found between IGF-1 and IGFBP-3 (r = 0.56; p = 0.0004) and between IGF-1 and GHBP (r = 0.34; p = 0.03) in the FSS group. However, in the normal-statured group only BMI and GHBP were correlated (r = 0.5; p = 0.02). CONCLUSIONS: These results strongly support the importance of the GH/IGF-1 functional axis in the pattern of growth and probably contribute to understanding of the pathophysiologic basis of the auxological differences found between groups.