We characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory results. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The enzymatic block was found at the beginning of steroidogenesis. The mutation was confirmed in the CYP11A1 gene. The patient is compound heterozygote for the novel CYP11A1 missense mutation c.412G>A (p.Gly138Arg) in exon 2 and frameshift mutation c.508_509delCT (p.Leu170Valfs*30) in exon 3. The CYP11A1: c.412G>A (p.Gly138Arg) was predicted as pathogenic by in silico analysis. So far, only 19 patients with CYP11A1 mutations causing P450scc deficiency have been reported worldwide. There are no related reports in the Czech Republic.

The prevalence rate of AD in AIT and first-degree relatives is high, and several new associations have been reported. Providers should be aware of comorbidities and TC in AIT as this would help in early diagnoses and timely interventions.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.

Background. The complete androgen insensitivity syndrome (CAIS) is a rare genetic disorder causing insensitivity to androgens in a person with female phenotype and 46,XY karyotype due to a mutation in the androgen receptor gene located on chromosome X. These children are born with female external genitalia, and females are transmitters. Case Report. We illustrate an unexpected diagnosis of CAIS in two siblings during examination for short stature, and describe transmission/carriers in the family along with ethical aspects. Conclusion. A genetic examination could have earlier revealed the transmission of c.2495G>Tp.(Arg832Leu) mutation in exon 7. Our experience highlights the possibility of prenatal testing for the management of pregnancy in a family with a history of CAIS. The implications of prenatal testing in relation to CAIS with clearer explication of ethical and clinical issues warrant further investigation.

Aim. To non-invasively identify the hemodynamic changes in critically ill children during the first 48 h following initiation of mechanical ventilation by the ultrasound cardiac output monitor (USCOM) method and compare the data in children with pulmonary and non-pulmonary pathology. Materials and Methods. This was a prospective observational study to evaluate the influence of mechanical ventilation on hemodynamic changes and to describe hemodynamic profiles of mechanically ventilated children. A total of 56 children with respiratory failure were included in the present study. Ventilated patients are divided into two groups. Group A (n=36) includes patients with pulmonary pathology. Group B (n=20) consists of patients with extra pulmonary etiology of respiratory failure. Hemodynamic parameters (cardiac index and systemic vascular resistance index) were evaluated using ultrasound cardiac output monitoring (USCOM 1A) immediately following initiation of mechanical ventilation and again at 6, 12, and 48 h. Pharmacological circulatory support (inotropes, vasopressors, levosimendan and phosphodiesterase III inhibitors) was individually and continuously modified based on real-time hemodynamic parameters and optimal fluid balance. Results. No significant differences in hemodynamic profiles were found between Group A and Group B. Conclusion. The protective strategy of mechanical ventilation was not associated with significant differences in hemodynamic profiles between children ventilated for pulmonary and non-pulmonary pathologies. Clinical Significance. Hemodynamically unstable children ventilated for pulmonary pathology with the protective strategy of mechanical ventilation had a greater requirement for inotropic and combined inotropic and vasoactive circulatory support than children ventilated for non-pulmonary causes of respiratory failure.

Applying LRAR would have reduced follow-up resulting in costsavings of £8,068; in total £9,718. Conclusion Implementing the LRAR in children presenting with AI in the UK is safe from a clinical view point; will reduce radiography and follow-up, resulting in significant cost-savings.