VI тип несовершенного остеогенеза. Наблюдение редкого случая

Osteogenesis imperfect is genetically heterogeneous group of diseases which are characterized by bone brittleness and fractures. It was thought for a long time that this is happening due to mutations in collagen genes. However, within past decade the understanding of osteogenesis imperfecta etiology has changed as a result of genetics development. The majority of all cases is related to mutations in collagen genes whereas rare mostly recessive forms are related to mutations in genes encoding collagen post-translational modification. Mutations in SERPINF1 gene were chosen as molecular cause of osteogenesis imperfecta type VI in 2011. Thus the new pathophysiology of this disease was revealed. Children with osteogenesis imperfecta type VI have high-frequency of fractures despite the management with bisphosphonates because mineralized bone osteoid is considerably reduced.Несовершенный остеогенез — генетически гетерогенная группа заболеваний, отличительной чертой которых являются хрупкость костей и переломы, возникающие, как считалось долгое время, вследствие мутаций в генах коллагена. Однако, в течение последнего десятилетия скачок в области генетических открытий обусловил появление новой парадигмы понимания этиологии несовершенного остеогенеза, где большинство случаев связано с наличием дефекта в коллагеновых генах, в то время как редкие, в основном рецессивные формы связаны с дефектами генов, влияющих на посттрансляционную модификацию коллагена. В 2011 г. мутации в гене SERPINF1 были идентифицированы в качестве молекулярной причины развития VI типа несовершенного остеогенеза, и тем самым, была выявлена новая патофизиология заболевания. Дети с несовершенным остеогенезом VI типа имеют высокую частоту переломов, несмотря на проведение стандартной терапии бисфосфонатами, т.к. площадь минерализованного остеоида кости при данном типе заболевания значительно уменьшена

ФАКТОРЫ РИСКА И МАРКЕРЫ НОЧНОЙ ГЕМОДИНАМИКИ ДЛЯ ПЕРСОНИФИЦИРОВАННОЙ ПРОФИЛАКТИКИ СЕРДЕЧНО-СОСУДИСТЫХ БОЛЕЗНЕЙ У ДЕТЕЙ

Background:  High mortality rates of cardiovascular disease request research revealing risk factors and early markers of cardiovascular dysfunction in children with chronic pathology.Objective:  to reveal the risk factors and early markers of night hemodynamic disorders for the development of personalized cardiovascular disease prevention in children based on the results of the combined daily monitoring of arterial pressure, ECG examination, and analysis of night sleep. Patients and methods:  Parents filled screeningquestionnaire of night sleep before the study onset. Combined monitoring and examination was performed  in 232  children aged 6–17 with different blood pressure disorders using Astrocard НS E2bp (Russia) equipment in the outpatient setting.Results: 24-hour BP monitoring identified arterial hypotension 3.8 times more often than routine ambulance method. 21% of children or every fifth child with hypotension  had night hypertension  associated  with maximum (93%) pathology  of ENT organs  with nasal obstruction. Differentiation of investigated groups by night PP and DBP show these marks of hemodynamics to be really important at the early period of pathology development in children. 62% of children had QT interval with bad adaptation to RR-interval at night. In the group with high BMI we found 1.6 times more often children with height more than 85th percentile of the norm. These children had night diastolic hypotension  5 times more often, children with obesity didn’t have normal 24-hour  BP dynamics, children with high BMI had longer QT-interval at night.Conclusions: We demonstrate the necessity of night sleep hemodynamics investigation in children for personalized cardiovascular disorder prevention. Children of early school age suffering from chronic ENT-pathology with nasal obstruction and/or high BMI, with high BMI, and with height ≥85th percentile of gender-age norm have risk of development of cardiovascular diseases.Обоснование.  Статистика  высокой смертности  от сердечно-сосудистых болезней  диктует  необходимость  поиска факторов  риска и ранних маркеров нарушения функции сердечно-сосудистой системы у детей с хронической патологией. Цель.  По результатам  комбинированного суточного мониторирования артериального  давления  (АД), электрокардиографического  исследования  (ЭКГ) и вопросникам сна изучить факторы  риска и ранние маркеры нарушения ночной гемодинамики с целью  развития  персонифицированной  профилактики  сердечно-сосудистых болезней у детей.Методы. Комбинированное суточное мониторирование АД и ЭКГ проведено 232 детям в возрасте 6–17 лет с различными нарушениями уровня АД с помощью прибора Astrocard НS E2bp (ЗАО «Медитек», Россия) в амбулаторных условиях. Перед исследованием  родителями  заполнялся  оригинальный скрининг-вопросник сна.Результаты. Артериальная гипотензия по результатам суточного мониторирования АД выявляется в 3,8 раза чаще, чем гипертензия, но 21% детей с дневной гипотензией имеют ночную гипертензию на фоне максимальной представленности хронической патологии ЛОР-органов (93 против 61% при гипотензии; р=0,049). Максимальные различия между  группами с различными  нарушениями АД отмечены по ночным пульсовому  (р<0,001)  и диастолическому (p<0,001) АД. У 62% детей из представленной  выборки удлинение интервала  QT на 0,06–0,16 сек выявлено преимущественно ночью, и значимо чаще при гипотензии (р=0,027).  При повышенном индексе массы тела в 1,6 раза чаще выявлялись дети ростом ≥85-го перцентиля нормы (p=0,040). У высоких детей в 5 раз чаще регистрировалась ночная диастолическая  гипотензия (р<0,001), при ожирении — отсутствовала нормальная суточная динамика АД, а при избыточной массе тела  более  выраженно  удлинялся  интервал  QT ночью (p=0,023). Заключение. Факторы риска развития сердечно-сосудистых болезней — хроническая патология ЛОР-органов, а также рост ребенка ≥85го перцентиля половозрастной нормы, особенно при повышенном индексе массы тела. Для персонифицированной профилактики  развития сердечно-сосудистых болезней у детей необходимо исследование ночной гемодинамики

Неврологические и нейрохирургические аспекты гипофосфатазии

Hypophosphatasia is a rare hereditary progressive disease caused by a mutation in ALPL gene and characterized by low activity of alkaline phosphatase. Due to the disruption of the bone mineralization process, ricket-like deformations of the skeleton occur in the clinic picture more frequently but other systemic manifestations can be also observed as respiratory insufficiency, urinary tract damage, and neurological disorders. Seizures, delayed physical and psychomotor development, attention deficit disorder, muscle weakness, fatigue, intracranial hypertension associated with the development of craniosynostosis are revealed in these patients. The severity of the disease depends on age: the highest mortality is reported in younger patients, in perinatal and infantile forms of hypophosphatasia. Diagnosis is based on the identification of specific clinical manifestations: retardation of growth and development, skeletal deformities, pain in muscles and joints, premature tooth loss. In laboratory tests, a steady decrease in alkaline phosphatase level is detected taking into account age and sex specification. If possible, alkaline phosphatase substrates are measured: levels of pyridoxal-5-phosphate in the blood and phosphoethanolamine in urine are higher at low enzyme activity. Radiographs of long bones typically reveal characteristic ‘tongues’ of lucency projecting from growth plates into metaphyses, hypomineralization, osteopenia, various kinds of deformation. All patients with suspected hypophosphatasia should be consulted by a clinical geneticist and evaluated to identify possible mutation in the ALPL gene.Гипофосфатазия — редкое наследственное прогрессирующее заболевание, вызванное мутацией в гене ALPL, вследствие которой угнетается активность щелочной фосфатазы. Из-за нарушения процесса минерализации костной ткани в клинической картине преобладают рахитоподобные деформации скелета, но зачастую возникают и другие системные проявления — нарушение дыхания, поражение мочевыделительной системы и неврологические расстройства. У пациентов выявляют судороги, задержку физического и психомоторного развития, дефицит внимания, мышечную слабость, быструю утомляемость, внутричерепную гипертензию, связанную с развитием краниосиностозов. Тяжесть гипофосфатазии зависит от времени ее манифестации: наибольшая смертность регистрируется при перинатальной и инфантильной формах заболевания. Диагностика основана на выявлении характерных клинических симптомов — задержки роста и развития, деформации скелета, болей в мышцах и суставах, преждевременного выпадения зубов. В лабораторных анализах отслеживается стойкое снижение уровня щелочной фосфатазы с учетом возраста и пола пациента; при низкой активности фермента уровни субстратов щелочной фосфатазы пиридоксаль-5-фосфат в крови и фосфоэтаноламина в моче всегда повышены. На рентгенограммах длинных трубчатых костей обнаруживаются «языки» просветления, проецирующиеся от зоны роста в метафизы, а также гипоминерализация, остеопения и другие деформации. Все пациенты с подозрением на гипофосфатазию должны быть проконсультированы клиническим генетиком и обследованы на выявление мутации в гене ALPL.КОНФЛИКТ ИНТЕРЕСОВАвторы декларируют отсутствие конфликтов интересов, связанных с публикацией настоящей статьи

Clinic Case of Rare Type VI Osteogenesis Imperfecta

Osteogenesis imperfect is genetically heterogeneous group of diseases which are characterized by bone brittleness and fractures. It was thought for a long time that this is happening due to mutations in collagen genes. However, within past decade the understanding of osteogenesis imperfecta etiology has changed as a result of genetics development. The majority of all cases is related to mutations in collagen genes whereas rare mostly recessive forms are related to mutations in genes encoding collagen post-translational modification. Mutations in SERPINF1 gene were chosen as molecular cause of osteogenesis imperfecta type VI in 2011. Thus the new pathophysiology of this disease was revealed. Children with osteogenesis imperfecta type VI have high-frequency of fractures despite the management with bisphosphonates because mineralized bone osteoid is considerably reduced

NIGHT HEMODYNAMIC DISORDER RISK FACTORS AND MARKERS FOR PATIENT-SPECIFIC APPROACH TO CARDIOVASCULAR DISEASE PREVENTION IN CHILDREN

Background:  High mortality rates of cardiovascular disease request research revealing risk factors and early markers of cardiovascular dysfunction in children with chronic pathology.Objective:  to reveal the risk factors and early markers of night hemodynamic disorders for the development of personalized cardiovascular disease prevention in children based on the results of the combined daily monitoring of arterial pressure, ECG examination, and analysis of night sleep. Patients and methods:  Parents filled screeningquestionnaire of night sleep before the study onset. Combined monitoring and examination was performed  in 232  children aged 6–17 with different blood pressure disorders using Astrocard НS E2bp (Russia) equipment in the outpatient setting.Results: 24-hour BP monitoring identified arterial hypotension 3.8 times more often than routine ambulance method. 21% of children or every fifth child with hypotension  had night hypertension  associated  with maximum (93%) pathology  of ENT organs  with nasal obstruction. Differentiation of investigated groups by night PP and DBP show these marks of hemodynamics to be really important at the early period of pathology development in children. 62% of children had QT interval with bad adaptation to RR-interval at night. In the group with high BMI we found 1.6 times more often children with height more than 85th percentile of the norm. These children had night diastolic hypotension  5 times more often, children with obesity didn’t have normal 24-hour  BP dynamics, children with high BMI had longer QT-interval at night.Conclusions: We demonstrate the necessity of night sleep hemodynamics investigation in children for personalized cardiovascular disorder prevention. Children of early school age suffering from chronic ENT-pathology with nasal obstruction and/or high BMI, with high BMI, and with height ≥85th percentile of gender-age norm have risk of development of cardiovascular diseases

Management of Children with Glycogen Storage Disease (Liver Involvement Forms). Best Practice Guidelines

Glycogen storage disease is the hereditary carbohydrate metabolism pathology which is caused by mutations in various genes encoding enzymes responsible for glycogenesis and glycogenolysis. Excessive glycogen deposition in various tissues cells (mostly in liver and muscles) occurs due to enzyme defects. The authors present recent epidemiological data and features of glycogen storage disease etiology and pathogenesis. Clinical characteristics of different types of this disease are also presented. The data on laboratory-instrumental and morphological signs of glycogen storage disease in children, as well as data on its treatment methods is provided in accordance with the developed clinical guidelines. The article provides relevant information on disease types with predominant liver involvement, besides the variety of clinical forms of glycogenosis

A non-interventional, prospective, multicenter study for evaluation of the use of the herbal medicinal product Canephron® N in the pediatric outpatient population in Russia

Abstract Background A herbal medicinal product (HMP) with centaury, lovage, and rosemary as active ingredients (brand name: Canephron® N) has been widely used for treatment and prevention of urinary tract infections (UTIs) and other urinary system disorders. Non-clinical in vitro and in vivo data indicate its diuretic, spasmolytic, anti-inflammatory, antioxidative and analgesic effects. The purpose of this non-interventional, prospective, multicenter study was to collect data on the use of the HMP in the Russian pediatric outpatient population. Results In total, 636 outpatients aged 1–17 years were enrolled. Of these, 634 received at least one dose of the HMP and were included in the safety set, which was used for analysis. 61 patients were 12–23 months, 227 were 2–5 years, 234 were 6–11 years and 112 were 12–17 years of age. The oral solution of the HMP was prescribed in 66.4%, and tablets (dragées) in 33.6% of the patients. For 48% of the patients the HMP was prescribed to treat an acute or chronic disease, 25% of the patients received it for prophylaxis, and 27% for both. More than half of the patients (53%) received the HMP as monotherapy. Main treatment indications were UTIs (34.1%) and pyelonephritis (30.0%). The proportion of UTIs was the highest within the youngest age group (51%), while the proportion of different cystitis forms increased in patients older than 2 years. Relevant proportions of different nephritis forms and urolithiasis were only observed in patients aged 12–17 years. Forms of cystitis were more frequent in female than in male patients (15% vs. 1%), while forms of nephritis, urolithiasis, and dysmetabolic nephropathy / crystalluria were more frequent in male patients. At the end of the observational period, 20% of the patients were reported as recovered from their disease, and 65% were reported to show improvements. For 91% of all patients with HMP monotherapy the investigators evaluated the effectiveness of the HMP as ‘good’ or ‘very good’. Nearly all patients (99%) evaluated the tolerability as ‘good‘or ‘very good‘. Five adverse drug reactions were observed. Conclusions The treatment of children aged 1–17 years with the HMP is safe and well tolerated. The study results support the use of the HMP for treatment and prophylaxis of urinary system diseases

Distal Tubulopathy. Liddle Syndrome

The clinical recommendations on management of children with Liddle syndrome which is characterized by severe hypertension along with low activity levels of renin and aldosterone in blood plasma, hypokalemia and metabolic alkalosis, were developed by the experts of the Union of pediatricians of Russia. Aspects of epidemiology, etiology and pathogenesis, disease progression, differential diagnostics and evidence-based treatment are presented

Loop tubulopathies: Bartter’s syndrome

The authors provide a review of current clinical guidelines regarding medical care provided to children with Bartter’s syndrome — impaired renal tubular function (loop of Henle) with the development of hypokalemia, hypochloremia, metabolic alkalosis and hyperreninemic hyperaldosteronism.  The specifics of disease epidemiology, etiology and pathogenesis  are described. The issues of differential diagnosis and treatment based on the principles of evidence are covered