[Continuous subcutaneous infusion of somatostatin analogues in the treatment of congenital hyperinsulinism].

BACKGROUND: Congenital hyperinsulinism (CHI) is a severe disease with a high risk of development of neurological complications due to persistent hypoglycemia. The use of an analog of somatostatin (octreotide) in patients with the resistance to the first-line drug allows to avoid surgical intervention. However, the octreotide is currently used in the form of frequent fractional injections due to the short duration of it’s effect. We present in this article our own experience of using octreotide in continuous subcutaneous infusion in pediatric patients in order to improve the quality of life. AIM To evaluate the efficiency and safety of the regime of continuous subcutaneous infusion of octreotide with the use of micro-dispensers (pumps) in children with diazoxide-resistant course of CHI. MATERIALS AND METHODS: An observational single-centre dynamic research was carried out on the basis of the Federal State Budgetary Institution «Endocrinology Research Centre» of the Ministry of Health of the Russian Federation. The study included pediatric patients with CHI and proven diazoxide-resistant course who were initially treated with octreotide in the form of intermittent subcutaneous injections. The researches compared the indicants of efficiency and safety of therapy on treatment of intermittent injections and after transfer to continuous subcutaneous infusion of the drug. The duration of each method of administration was at least 2 weeks. RESULTS: 16 patients took part in the research. The median for the total duration of octreotide usage in the examined patients was 3 months. According to the results of the work, the use of micro-dispensers for continuous subcutaneous administration of octreotide allowed to reduce the number of patients with episodes of hypoglycemia for more than 4 times (13/16 vs. 3/16); p=0,001). Also, there was a significant decrease in the number of patients with hyperglycemic episodes (4/16 vs. 0/16); p=0.000) and reduced dose of intravenous glucose (6.8 vs 5.2 mg/kg/min; p=0.042) as a result of continuous therapy, which indicates the advantages of smooth continuous administration comparing to single injections. We have not detected any significant side effects of the treatment. Elevated liver enzyme levels, dyspeptic symptoms and gallstone formation in some patients did not require cancellation of therapy. There were no hormonal disorders in the form of hypothyroidism and somatotropic hormone deficiency against the background of continuous octreotide infusion. CONCLUSIONS: Thus, the use of octreotide in patients with diazoxide-resistant course of СHI in continuous subcutaneous infusion using pumps has a number of advantages over the standard method of intermittent subcutaneous injection. This method of administration allows to achieve better glycemic control and reduce the risks from infusion therapy with highly concentrated glucose solutions, which undoubtedly improves the quality of life of patients.

[Transient hyperinsulinism in neonates].

Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.

Hepatic glycogen synthase (GYS2) deficiency: seven novel patients and seven novel variants.

Glycogen storage disease type 0 (GSD 0) is an autosomal recessive disorder of glycogen metabolism caused by mutations in the GYS2 gene manifesting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting, and postprandial hyperglycemia and hyperlactatemia. GSD 0 is a rare form of hepatic glycogen storage disease with less than 30 reported patients in the literature so far.DNA samples of 93 Russian patients with clinical diagnoses of hepatic GSDs were collected and analyzed by next-generation sequencing custom target panel and by direct sequencing. Seven new GSD 0 patients with variable phenotypes were found showing 10 variants. Seven variants are novel.We present seven new GSD 0 patients with variable phenotypes. Overall, 10 different mutant alleles of the GYS2 gene were found. Seven of them are novel: c.214delC, c.845delT, c.1644C>A, c.205T>A, c.929G>T, c.1169G>C and c.1703C>A. Three of the novel variants were annotated as pathogenic and likely pathogenic; four other variants have an uncertain significance.The current results expand the spectrum of known mutations in GYS2 and suggest that phenotypes of GSD 0 are more variable and less specific than the reported ones. SYNOPSIS: Seven new patients with glycogen storage disease type 0 were found using next-generation sequencing and seven novel variants of GYS2 gene were annotated.

Response of pure red cell aplasia to cyclophosphamide after failure of mycofenolate mofetil in a patient with polyglandular syndrome type I.

A 26-year-old female with the classic major and minor components of autoimmune polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia. Treatment with 1.5 g/d mycofenolate mofetil for 3 months failed to restore erythroid production. Treatment with cyclosporine A produced a good partial response but led to renal toxicity and was therefore substituted with cyclophosphamide, which had a good partial effect and lasted for 18 months. The relapse of anemia was not observed during the 6-month follow-up period after the cessation of treatment.