Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife.

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of X-linked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing the COL4A5 locus on chromosome X was assessed. All G624D alleles were found on the same rare haplotype background, indicating a founder effect dating back to the 12-13th century. The phenotypic data of 131 children with X-linked Alport Syndrome and their 195 affected adult relatives revealed that the G624D variant was associated with a significantly milder clinical course in comparison to other pathogenic COL4A5 variants. Furthermore the clinical course of this genetically uniform cohort was milder than that observed in individuals with other COL4A5 missense mutations. In spite of the benign clinical manifestation throughout childhood and early adulthood, the G624D variant confers significant risk for both kidney failure and deafness in males, albeit 20-30 years later than that observed in individuals with other COL4A5 pathogenic variants (50% cumulative risk of starting dialysis at 54 years (95% confidence interval: 50-62) v. 26 years (95% confidence interval: 22-30)). Thus, males with G624D are candidates for existing and emerging therapies for Alport Syndrome.

Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127-FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

Hyperbaric oxygenation in pediatrics: indications in the light of evidence - based medicine.

Hyperbaric oxygen therapy (HBOT), which is a centuries-old treatment, has now increasingly often been used in the pediatric population. The basic indications for HBOT are well-known disease entities, i.e. carbon monoxide poisoning or decompression sickness. Due to the immunomodulatory properties of hyperbaric oxygen, attempts are made to use HBOT in the treatment of atopic dermatitis or inflammatory bowel diseases. The close cooperation between pediatricians and hyperbaric medicine teams is very important to obtain optimal results. The aim of this article is to present the mechanism of hyperbaric oxygen activity, and its influence on selected disease entities. The paper outlines new perspectives for HBOT in the pediatric population.