SYNGAP1 and Methylenetetrahydrofolate in Cerebrospinal Fluid: Cognitive Development after Oral Folate (5-Methyltetrahydrofolate) Supplementation in a 5-Year-Old Girl

Synaptic Ras GTPase-activating protein 1 (SYNGAP1), also called Ras-GAP 1 or RASA5, is a cerebral protein with a role in brain synaptic function. Its expression affects the development, structure, function, and plasticity of neurons. Mutations in the gene cause a neurodevelopment disorder termed mental retardation-type 5, also called SYNGAP1 syndrome. This syndrome can cause many neurological symptoms including pharmaco-resistant epilepsy, intellectual disability, language delay, and autism spectrum disorder. The syndrome naturally evolves as epileptic encephalopathy with handicap and low intellectual level. A treatment to control epilepsy, limit any decrease in social capacities, and improve intellectual development is really a challenging goal for these patients. The etiologic investigation performed in a 5-year-old girl with early epileptic absence seizures (onset at 6 months) and psychomotor delay (language) revealed a low methylenetetrahydrofolate level in cerebrospinal fluid in a lumbar puncture, confirmed by a second one (35 nmol/L and 50 nmol/L vs. 60–100 nmol/L normal), associated with normal blood and erythrocyte folate levels. Hyperhomocysteinemia, de vivo disease, and other metabolic syndromes were excluded by metabolic analysis. No genetic disorders (like methylenetetrahydrofolate reductase and methenyltetrahydrofolate synthetase) with folate metabolism were found. The physical examination showed only a minor kinetic ataxia. An oral folate (5-methyltetrahydrofolate) supplementation was started with oral vitamin therapy. The child showed good progress in language with this new treatment; epilepsy was well balanced with only one antiepileptic drug. The SYNGAP1 mutation was identified in this patient's genetic analysis. Since the start of folate supplementation/vitamin therapy, the patient's neurologic development has improved. To our knowledge, no association between these two pathologies has been linked and no patient with this SYNGAP1 mutation has ever showed much intellectual progress. Low cerebral methylenetetrahydrofolate levels could be associated with SYNGAP1 mutations. One of the hypotheses is the link of folate metabolism with epigenetic changes including methylation process. One inborn metabolic activity in folate metabolism may be associated with SYNGAP1 disease with epigenetic repercussions. Further studies should assess the link of SYNGAP1 and methyltetrahydrofolate and the evolution of SYNGAP1 patients with oral folate supplementation or vitamin therapy.

P076 SARS-COV-2 infection in two patients with juvenile lupus

Background The new SARS-COV-2 pandemic affects both children and adults, with a low pediatric percentage of < 1%. The severity and death rate of this disease are lower in this age range. The pediatric populations who are most likely to develop severe COVID 19 are those with particularly immunosuppressive comorbidities. Juvenile systemic lupus erythematosus “jSLE” which represents the prototype of autoimmune diseases, constitutes a predisposing ground for severe viral infections, related to immune dysfunction; linked on one hand to the disease, and on the other hand to the numerous immunosuppressive treatments prescribed. In this context, a great risk was incurred by patients with jSLE. The aim of this work is to assess the severity of COVID 19 infection in our patients with jSLE Methods and results Among 20 cases of jSLE hospitalized during the year 2020, we report 2 medical cases report of patients aged 9 and 8, respectively, followed-up in our tertiary care unit for jLES based on the criteria of the Systemic Lupus International Collaborating Clinics “SLICC 2012” and the American College of Rheumatology “ACR 2019”, and who developed a cough, progressing dyspnea and feverish. The Covid 19 was confirmed by a positive PCR for SARS-COV-2. The chest X-ray showed a systematized right cavity in 1 case. Thoracic CT showed foci of alveolar condensation systematized with air bronchogram sign extended to > 25%, associated with bilateral subpleural ground glass areas centrally and peripherally compatible with moderate pneumonia type COVID 19 in one case. The patients were in flare of their lupus disease, proven by the consumption of the C3 and C4 fractions of the complement. They were treated according to the national COVID 19 infection management plan comprising azithromycin at a dose of 20 mg/kg/day on D1 then 10 mg/kg/day for 6 days, increasing the doses of hydroxychloroquine, associated with vitamin therapy (vitamin C, Zinc, vitamin D), the evolution was favorable after 7 days of treatment. Conclusion Reassuringly, several studies have shown that the clinical course of covid 19 in SLE does not appear to be more severe than in the general population. The hydroxychloroquine prescribed routinely in patients with SLE does not protect against covid 19, but may prevent the occurrence of severe forms.

COMPARATIVE EFFECTIVENESS OF VARIOUS SCHEMES OF IMMUNOREHABILITATION IN INFERTILITY OF TUBOPERITONEAL GENESIS

The study aimed to compare the effectiveness of various pharmacotherapy regimens for infertility of tubo-peritoneal genesis. Under constant supervision were 96 patients referred to the hospital for diagnostic laparoscopy for infertility of tubo-peritoneal genesis, divided equally into 4 groups depending on the pharmacological treatment methods: the 1st group received basic pharmacotherapy (BPT) after endoscopic surgery (antibacterial, antifungal, vitamin therapy). Patients of groups 2-4, in addition to BPT, received Hepon, Cycloferon or Lavomax, respectively. The control group consisted of 38 gynecologically healthy women. Laboratory examination was performed within 24 hours after the operation and on the 30th day after BPT. Vaginocervical lavage and plasma were assayed for the activity of lipid peroxidation processes, the state of the antioxidant system, the level of stable nitric oxide metabolites, neopterin, C-reactive protein, cytokines (TNFα, IL-1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA, sIgA), components of the complement system (C3, C4, C5, C5А), phagocytic and oxygen-dependent activity of polymorphonuclear leukocytes. It was established that the use of immunomodulatory and antiviral activity medication with BPT according to the degree of increasing efficiency in the correction of immunometabolic laboratory parameters at the systemic and local level in infertility of tuboperitoneal genesis is as the following sequence: basic pharmacotherapy < basic pharmacotherapy + Hepon < basic pharmacotherapy + Cycloferon < basic pharmacotherapy + Lavomax.

ENDOMETRIAL RECEPTIVITY AS THE KEY TO THE SUCCESS OF ART PROGRAMS: A LITERATURE REVIEW

Relevance: To date, the success of in vitro fertilization (IVF) programs in Kazakhstan is 38%. The purpose of the study was to evaluate the mechanisms of influence of various risk factors on endometrial receptivity in women in IVF programs. Materials and Methods: This review was based on a search conducted for domestic and foreign publications available in Russian and international search systems (PubMed, eLibrary) for the past 25 years. Results: Chronic endometritis is a verified cause of impaired receptivity. Many studies have proven the beneficial effect of complex empirical treatment using antibacterial, anti-inflammatory, hormonal therapy with transdermal forms of estrogens and vitamin therapy on the outcome of IVF. Conclusion: The problem of recurrent implantation disorders in IVF programs is multifactorial. Women with unrealized reproductive function require rehabilitation after an unsuccessful fertilization attempt to prevent disorders of homeostasis and ensure adequate pain relief during transvaginal puncture of ovarian follicles. In addition to hormone therapy with transdermal forms of estradiol, complex rehabilitation measures shall include immunomodulatory therapy, psychotherapy, and vitamin therapy.

COVID-19 – doctor and patient. Clinical case

COVID-19 was initially described as a viral pneumonia because it produced an acute and possibly fatal respiratory distress. Later, however, other types of COVID-19 symptomatology were described, but also nonspecific: gastrointestinal, neurological, dermatological and even psychiatric. Therefore, to establish a definite diagnosis, a PCR test is needed to detect the virus on the nasopharyngeal mucosa. The treatment is not yet a specific one (there is no specific antiviral etiological treatment), being rather symptomatic (antipyretic, anti-inflammatory, antitussive etc.) and with the prophylaxis of complications (anticoagulant and antibiotic therapy, respiratory support, vitamin therapy).

A Comprehensive Program of Psychological, Pedagogical and Medical Rehabilitation Assistance to Children Affected from Hostilities and Armed Conflicts “Andryushka”

The complex program of psychological, pedagogical and medical rehabilitation assistance to chil-dren affected by military operations and armed conflicts “Andryushka” was created with the aim of providing differentiated comprehensive psychological, medical, social and rehabilitation assistance to children with disabilities from combat zones and armed conflicts. The program is distinguished by the complex nature of psychological and pedagogical support, the presence of a course of medical, cultural and environmental rehabilitation. All program participants during the day receive psychologi-cal, pedagogical and speech therapy assistance, attend master classes, cultural and leisure activities, museums and exhibition complexes, undergo comprehensive medical rehabilitation: medical examinations, medical massage, exercise therapy, balneo- and speleotherapy , mechano- and ergo-therapy, vitamin therapy, robotic and computerized rehabilitation, locomotor therapy, physiotherapeutic and drug treatment in accordance with doctors’ prescriptions, etc. drawing up an individual escort plan (2 days); stage of active psychological and pedagogical, defectology and speech therapy support of cultural, environmental and medical rehabilitation of program participants (17 days); the stage of the final comprehensive psychological, medical, social and medical examination of the program participants with the preparation of recommendations for parents on the further support and re-habilitation of children (2 days). The total duration of the program is 21 days.