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Kabuki syndrome is a rare hereditary disease characterized by distinctive facial features, skeletal abnormalities, mental retardation, developmental delay, and anomalies in multiple organ systems development.Congenital hyperinsulinism is a rare manifestation of his Kabuki syndrome. However, early diagnosis is crucial to prevent neurological complications of hypoglycemia.There are 2 types of Kabuki Syndrome depending on severity of symptoms. Kabuki syndrome Type 1 is associated with heterozygous mutations in gene KMT2D. Kabuki syndrome Type 2 is inherited in an X-linked manner. It’s associated with heterozygous mutations in gene KDM6A and characterized by more severe course of the disease.This paper presents 2 cases of children with congenital hyperinsulinism as the feature of Kabuki syndrome Type 1 and Type 2.

Introduction. Congenital hyperinsulinism (CHI) is an inherited disease characterized by severe persistent hypoglycemia in the neonatal period due to insulin hypersecretion and rapid development of neurologic and systemic disorders. There are two main CHI forms: a diffuse one when hyper functioning of beta-cells affect the whole pancreas, and a focal one, characterized by an area of intact parenchyma. Currently, surgery is an acknowledged approach in focal forms, while in diffuse CHI forms surgical treatment is prescribed only in severe pharmacoresistant cases.Material and methods. A total of 11 patents with CHI, aged 1.5 - 26 months, had laparoscopic pancreatic resections at the department of pediatric surgery of Russian Medical Academy of Continuous Professional Education. All patients were examined , treated and prepared for surgery at the Endocrinology Research Centre ( Moscow). The focal CHI form was diagnosed in 3 children; the diffuse one - in 8 patients. In the focal CHI form, a focal resection was done: laparoscopic corpocaudal resection of the pancreas – 2 patients; resection of the pancreatic head with Roux–en-Y pancreaticojejunostomosis - 1 child. All children with diffused disease had laparoscopic near-total (98%) pancreatectomy.Results. In all cases, there were no intraoperative complications. Stenosis of the distal common bile duct developed in one child after the resection of pancreatic head which required a laparoscopic cholecystoduodenoanastomosis. There were no other complications. Two children with focal CHI were reported to recover completely; one patient suffered of hypoglycemia attacks not related to the increased insulin production. In diffuse cases, a stable euglycemia was achieved in 2 patients; 3 children had recurrent hypoglycemia attacks which required Somatostatin analogue therapy. One patient developed diabetes mellitus. In this case, follow-up period lasted for 2 months which is too short to assess the endocrinological outcome.Conclusion. The article presents the first Russian experience of laparoscopic pancreas resection in children with CHI. The laparoscopic approachcan be successfully applied in the surgical treatment of children with CHI.

Donohue syndrome (DS), also called Leprechaunism, is the most severe form of insulin resistance associated with biallelic mutations in INSR gene (OMIM: 147670). The approximate incidence of this syndrome is 1 per 1000000 births. Patients are present with typical clinical features such as intrauterine growth retardation, facial dysmorphism, severe metabolic disturbances, hepatomegaly and hypertrophic cardiomyopathy. Most DS patients die within the first two years of life due to respiratory infections, severe hypoglycemia or progressive cardiomyopathy. Treatment options are limited and no specific therapy exist for DS. Given the similarities between insulin and insulin-like growth factor 1 (IGF-1) receptors, recombinant human IGF-1 (rhIGF-1) has been used to treat severe insulin resistance including DS.We report the case of a male patient with genetically confirmed Donohue syndrome, successfully treated with continuous subcutaneous IGF1 infusion via insulin pump. We observed improvement of glycemic control, liver function and cardiac hypertrophy regression following 15-month IGF1 therapy.

BACKGROUND: Children with congenital hyperinsulinism (CHI), a severe orphan disease, are still one of the most demanding patients in the endocrinology practice. The use of first- and second-line drugs is not always effective and has a number of restrictions. Lanreotide — long-acting somatostatin — represents an alternative insulinostatic therapy. The main advantage of lanreotide is stable concentration of the drug in the blood that enables minimizing the number of injections. However, the experience of using lanreotide in the treatment of CHI is limited to small groups of patients. There is also a problem of the absence of a standardized regimen in clinical practice; and the calculator for evaluating the initial effective drug dose is needed.AIM of the study is to evaluate the effectiveness and safety of lanreotide therapy in the treatment of CHI in children.MATERIALS AND METHODS: An open single-center observational study was conducted on the basis of Endocrinology Research Centre. The study included diazoxide-unresponsive pediatric patients with CHI who were initially treated with octreotide in different modes: multiple daily subcutaneous injections or continuous subcutaneous infusion via pumps. The indicators of the effectiveness and safety of the lanreotide therapy were evaluated shortly after the first injection and lately on a regular visit after further injections.RESULTS: The study group included 12 patients. Persistent euglycaemia was achieved in 67% of the subjects (8/12). Complete effectiveness of the therapy was observed in 8/12 patients (67%), partial — in 3/12 (25%), and lack of effectiveness — in 1/12 of the patient (8%). The age of the patients at the time of lanreotide administration was 6 months (5; 15). According to the study, the most effective dose of lanreotide is 3.5-5.5 mg/ kg/ month. There were no significant side effects observed.CONCLUSIONS: The use of lanreotide in patients with diazoxide-resistant congenital hyperinsulinism was effective and safe in the vast majority of the patients. Moreover, we were able to calculate the effective dosage of lanreotide in CHI patients which fulfilled the clinical demand.

Работы, представленные на конгрессах, наглядно демонстрируют существенный прогресс в изучении генетических аспектов сахарного диабета. Как справедливо заметил Т.Г. Барретт, еще 15 лет назад сахарный диабет у детей было принято считать диабетом 1 типа, и при наличии осмотических симптомов у ребенка необходимость в дифференциальной диагностике отпадала. Со временем диабет, ассоциированный с внепанкратическими проявлениями, стал характеризоваться как синдром. Были выявлены генетические нарушения, стали возможными диагностические тесты и появилось специфическое лечение?.

Objective Hypoglycemia in congenital hyperinsulinism (CHI) in children increases the risk of brain damage, seizures and development delay. Aim was evaluate the frequency of epilepsy, development delay and neurological manifestations in children with CHI. Methods Clinical, EEG, MRI, genetic, psychological testing. Results 8 boys and 7 girls with CHI aged from 5 month to 7 years (on average 3 years 3 months) were examined. Hypoglycemia was found one the first week of life in 10 children, before 12 month – 5. It was manifested as seizures in 10 of 15 patients (66%). During the follow-up epilepsy developed in 3 patients (20%) and antiepileptic drugs were prescribed. On the neurological examination 6 children had only mild changes, 3 – cerebral palsy (60%). Brain MRI revealed abnormalities in 8 (53%) cases: 7 – atrophy of different localization. Epileptiform abnormalities on the EEG were registered in 4 cases, bifrontal slowdown – in other 5 cases. On psychological testing performed in 9 of 15 patients development delay was observed, which was mild in 2, moderate – in 3, severe – in 4. Before the CHI diagnosing 5 children received anticonvulsive therapy, which was ineffective in all cases before starting specific therapy. The genetic assessment was done in 13 children: in 2 cases the KCNJ11 gene mutation was found, in 4 – ABCC8 gene mutation. Children with ABCC8 gene mutation had more complicated course of CHI, 2 of them had epilepsy, 3 – severe development delay. Conclusion The seizures in CHI do not always require diagnosing “epilepsy” and prescription of antiepileptic drugs. EEG abnormalities in these children may be observed despite of the absence of epileptic seizures. Development delay was more often revealed in children with abnormalities on neurologic examination and MRI. Children with ABCC8 gene mutation have more complicated course of CHI and more prominent development delay.

We studied the dynamics of bone tissue mineralization in the pores of a titanium matrix and the mechanical properties of the resulting titanium-bone tissue composite. It is shown that the mineralization process is virtually accomplished within six months after implantation of a porous titanium article into the organism. As the pores and channels in the titanium matrix are filled with bone tissue, the material becomes a composite with mechanical properties higher as compared to those of the porous implant or bone tissue.

It has been established that the interaction of hydroxyapatite with titanium nickelide and titanium results in the formation of new phases whose physicomechanical properties and biocompatibility are unknown. After hydroxyapatite has been resorbed, these phases come in contact with tissue and near-tissue fluids and influence the result of the implant.