The cystic fibrosis transmembrane regulator (CFTR) gene encodes the synthesis of a protein of the same name, which functions as a direct activator of anionic transport. Chloride is the most abundant anion; as an antagonist of Na+ and K+, it provides electroneutrality of cell membranes at rest; together with cations, it serves as an important osmolyte and forms water flow across cell membranes for transepithelial secretion.Glandular cells in CF trap Cl– and Na+, and the prodused secretion is excessively viscous. Subnormal CFTR activity leads to stagnation of mucociliary clearance, inhibition of intestinal transport.In addition to exocrine disorders, CFTR mutations are associated with a decrease in volume, mass, increased apoptosis of β-cells of the pancreas, a significant suppression of insulin exocytosis in response to stimulation with glucose and glucagon-like peptide-1, hyperglucagonemia against the background of a defect in the suppression of α-cell function by insulin, but a decrease in maximum capacity α-cells.Deficiency and progressive decline in bone mineral density is an expected secondary manifestation of CF due to pancreatic exocrine insufficiency with malabsorption of nutrients and fat-soluble vitamins. However, in patients with the F508del mutation, a significant decrease in the synthesis of OPG, COX-2, PGE2 in the osteoblastic formation, and an increase in the activity of the antianabolic NF-kB were found. We are talking about a defect in the canonical signaling pathway (Wnt/β-catenin), which regulates the expression of genes-activators of osteoblastogenesis, dissociation of the stages of physiological bone remodeling.In addition to congenital bilateral or unilateral aplasia of the vas deferens, an increase in the frequency of CFTR mutations is also found in non-obstructive azoospermia, oligo-, astheno- and teratospermia. CFTR is involved in the entry of HCO3– into Sertoli cells to trigger cAMP-dependent transcription and its defects lead to suppression of FSH-dependent gene expression of spermatogenesis, loss of sequence in the Wnt cascade, destruction of the PGE2-dependent transepithelial interaction and, as a consequence, the blood-testicular barrier.CF is characterized, along with classical signs, by endocrine dysfunction of the pancreas, osteoporosis with suppression of osteoblastogenesis, and a defect in spermatogenesis.
We present a case of a teenage boy with a Rabson-Mendenhall syndrome. There are only few recent publications on the topic of Rabson-Mendenhall syndrome in medical literature. This syndrome appears with a same frequency in both sexes. The disease prevalence is still unknown due to many undiagnosed cases linked with high mortality in early childhood. There are no prenatal screening for this disease till now, but it is clear, that in case of positive diagnostic tests, abortion should be recommended. The typical clinical symptoms of Rabson-Mendenhall syndrome are the following: physical development delay, loss of subcutaneous fat, teeth and nails abnormalities (premature teeth eruption, teeth number doubling, nails thickening). The earliest signs of the syndrome are skin hyperpigmentation and hyperkeratosis at neck, armpits and groin, which are typical for insulin resistance. Children with Rabson-Mendenhall syndrome usually have early manifestation of diabetes mellitus, characterized by labile disease course and frequent ketoacidosis state. The present clinical case might be interesting regarding a long follow-up of the child.
The article presents the modern views of clinicians and geneticists on one of the most severe genetic disorders of skeletal and connective tissues - osteogenesis imperfecta. The review provided the literature data that showed the incidence rates, genetic heterogeneity of osteogenesis imperfecta, as well as the role of some proteins involved in the construction of bone tissue, as well as a clinical classification of the main types of the disorder. The authors described a clinical case: a girl with typical clinical and radiological manifestations of the rarest of all types of osteogenesis imperfecta - type II (perinatal-lethal, congenital osteogenesis imperfecta, Vrolik’s syndrome). The child’s diagnosis was verified by a parallel DNA sequence analysis which showed a heterozygous mutation in exon 29 (c.1966G> A) of COL1A1 gene not previously described in the literature. It caused the substitution of glycine for serine at position 656. The role of antenatal diagnostics and the importance of medical genetic counselling of the family before planning the next pregnancy due to the existing risk of re-birth of a sick child is outlined. Due to the fact that majority of the patients with the most prognostically unfavourable type II osteogenesis imperfecta, as a rule, die in utero, the described case of observation of the girl with typical clinical and X-ray signs of the disorder for almost 3 months of postpartum period is extremely rare and highly indicative. The detection of the heterozygous mutation in exon 29 (c.1966G > A) of COL1A1 gene by a parallel DNA sequence analysis which was not previously described in the literature gives an additional significance to the described observation.
The article presents the results of vitamin D tests in children with cystic fibrosis and in healthy children living in the South of Russia. The study showed the high prevalence of vitamin D deficiency and inadequate levels in patients with cystic fibrosis (86.7%). 25(OH) D level characterizing the vitamin D status decreases progressively in patients and healthy children. With regard to the above mentioned, it is significantly lower in patients with cystic fibrosis than in healthy children in all age periods. The correlation between the serum calcidiol level and the age of patients with cystic fibrosis was r = -0.44 (p = 0.015). Intake of prophylactic (500--1000 IU/day) and therapeutic (1500--3000 IU/day) doses of cholecalciferol results in a less significant increase in calcidiol levels in patients with cystic fibrosis compared with healthy children. A significantly lower 25(OH)D level was detected in patients with cystic fibrosis infected withStaph. aureus.The 25(OH)D levels are significantly lower in children with cystic fibrosis and hypocholesterolemia, than in patients with normal cholesterol levels. Risk factors for the development of severe hypovitaminosis D in children with cystic fibrosis are age, physical developmental delay, exocrine pancreatic insufficiency, presence of chronicStaph. Aureusbronchopulmonary infection. Given the conducted study, the dosage of cholecalciferol in patients with cystic fibrosis should be at least 2 times higher than that in healthy children.
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