In Search of Spinal Muscular Atrophy Disease Modifiers.

The 5q Spinal Muscular Atrophy (SMA) is a hereditary autosomal recessive disease caused by defects in the survival motor neuron () gene encoding survival motor neuron (SMN) protein. Currently, it is the leading cause of infantile mortality worldwide. SMA is a progressive neurodegenerative disease with "continuum of clinical severity", which can be modulated by genetic and epigenetic factors known as disease modifiers (DMs).

Genotype-Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants.

Background: Fabry disease (FD) is a rare hereditary multisystem disease caused by variants of the gene. Determination of gene variants and identification of genotype-phenotype correlations allow us to explain the features of FD associated with predominant damage of one or another system, both in the classical and atypical forms of FD, as well as in cases with late manifestation and involvement of one of the systems.

Methods: The study included 293 Russian patients with pathogenic variants of the gene, which were identified as a result of various selective screening programs.

Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population.

(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease.

[Multilevel botulinum toxin treatment in severe spastic forms of cerebral palsy (GMFCS IV-V)].

Objective: To evaluate the most typical target muscles and dosages for the first and repeated botulinum toxin A (BTA) injections in cerebral palsy (CP) patients with severe motor deficit - GMFCS IV-V.

Material And Methods: A retrospective analysis of 677 protocols of the first and repeated Abobotulinumtoxin A (AboA) injections in 333 patients with CP GMFCS IV and V, aged 1 to 18 years, was carried out.

Results: Ninety-seven percent of patients received multilevel injections.

[Botulinum toxin type A (Incobotulinum toxin A) in spastic forms of cerebral palsy: a retrospective analysis of clinical experience].

Objective: A retrospective analysis of the experience of using Incobotulinum toxin A injections for the treatment of spasticity in children with cerebral palsy (CP).

Material And Methods: One hundred and eighty-five children with spastic forms of CP, including 114 boys (61,6%), were studied. The average age of the patients was 3,8±2,5 years; the average weight was 14,2±6,9.

[Changes of the spasticity patterns in children with cerebral palsy GMFCS III at the age of 2 to 12 years].

Unlabelled: Spastic muscles in the pathological motor patterns may change at different ages that leads to the changes in anti-spastic treatment.

Objective: To study the specific patterns of spasticity in CP patients with level III according to the Gross Motor Function Classification System (GMFCS) in different age periods.

Material And Methods: A retrospective analysis of injection protocols of Abobotulinum toxin A for 99 patients with bilateral spastic CP GMFCS III at the age of 2 to 12 years was performed.

[Efficacy and safety of botulinum toxin type A (IncobotulinumtoxinA) in the treatment of patients with cerebral palsy].

Aim: To assess the safety and clinical and neurophysiological efficacy of xeomin in children with spastic equinus and equinovarus foot deformity in cerebral palsy.

Material And Methods: Sixty-four patients with spastic forms of cerebral palsy (levels I-IV on the GMFCS) were enrolled into this multi-center open-label comparative randomized trial. The patients were administered xeomin or botox once, each drug being administered to 32 patients.

[Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid].

Aim: To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups.

Material And Methods: One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group.

[The First Russian Consensus on the Multilevel Abobotulinumtoxin A Injections in Spastic Forms of Cerebral Palsy].

Spasticity treatment is one of the key aspects of the contemporary cerebral palsy (CP) rehabilitation that influences on the effectiveness of other methods. The paper presents the first Russian document that unites the recommendations for the BTA treatment of CP and could be used as the guideline for the multilevel injections. The Russian consensus on the multilevel botulinum toxin A (BTA) treatment of spastic CP is based on the international data and the results of national studies.

[Evaluation of physical development in children with classical phenylketonuria].

Classical phenylketonuria (PKU) is hereditary disease, which is based on the disturbance of phenylalanine conversion to tyrosine. The basic treatment of PKU is low phenylalanine diet. Prolonged restriction of natural protein may have a negative impact to PKU patient growth and physical development.

[Sanfilippo Syndrome].

Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system.

[Selection of a dose of the botulinum toxin A in spastic forms of cerebral palsy].

Aim: To analyze the efficacy and safety of dose ranges of abobotulinum toxin A (BTA) for multilevel injections into upper and lower extremity muscles in children with spastic forms of cerebral palsy (CP).

Material And Methods: We analyzed retrospectively multilevel BTA injections for 216 patients, aged from 2 to 17 years. Children received 1-6 repeated injections and complex physiotherapy.

[Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].

Background: Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products.

Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia.

Background: The mucopolysaccharidoses (MPSs) are rare genetic disorders caused by mutations in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). In this study, we analyzed a total of 48 patients including MPSI (n=6), MPSII (n=18), MPSIIIA (n=11), MPSIVA (n=3), and MPSVI (n=10).

Methods: In MPS patients, urinary GAGs were colorimetrically assayed.

Genetic analysis of 17 children with Hunter syndrome: identification and functional characterization of four novel mutations in the iduronate-2-sulfatase gene.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked disorder caused by alterations in the iduronate-2-sulfatase (IDS) gene. In this study, IDS activity in peripheral mononuclear blood monocytes (PMBCs) was measured with a fluorimetric enzyme assay. Urinary glycosaminoglycans (GAGs) were quantified using a colorimetric assay.

[The use of topiramate in the treatment of focal epilepsy in children].

Topiramate was used in the treatment of 66 children, aged 2--16 years (mean age 7.0±4.6 years), including 19 patients with idiopathic form of focal epilepsy (IFE), 21 patients with cryptogenic forms (CFE) and 26 patients with symptomatic forms (SFE).

[Assessment of the life quality in children with phenylketonuria].

Background: Phenylketonuria (PKU) - the most common inherited disorder of amino acid metabolism, identified in Russia by neonatal screening. The results of dietary treatment demonstrate a positive effect. However, the quality of PKU patients life remains unknown.

[Case of combination of Beckwith-Wiedemann syndrome with West syndrome].

Beckwith-Wiedemann syndrome (BWS) is etiologically connected with genetic/epigenetic growth dysregulation. The supposed localization of this disorder is a short arm of chromosome 11 (11p 15.5).

[Clinical experience of the repeated multilevel injections of the botulinum toxin type A (abobotulinum toxin A) in the spastic forms of cerebral palsy].

Objective: Our aim was to analyze the dosages of Abobotulinum toxin A used for each muscle in the clinically effective and safe repeated multilevel injections in CP children, and the intervals between injections.

Methods: Retrospective analysis of 229 injection sessions into 359 muscles of the upper and 361 muscles of the lower extremities in 133 children (2-18 years) with spastic CP. Analysis included only patients who were injected for the first time and demonstrated decrease of spasticity in injected muscles according to modified Ashworth and/or Tardieu scales without significant side effects 2-4 weeks after injections.

[Differential diagnosis of multiple sclerosis with pediatric onset: the experience of the Moscow Division for treatment of children and adolescents with multiple sclerosis].

The diagnosis of multiple sclerosis in children and adolescence should be differentiated from a group of rare white matter diseases, with fuzzy diagnostic criteria. Some of these conditions require modern diagnostic techniques and wide knowledge of the doctor. The Moscow Division for treatment of children and adolescents with multiple sclerosis is a specialized advisory structure, which has specialists with experience in the differential diagnosis of multiple sclerosis with pediatric onset.

[An electromyographic study on the development of optimal tactics of botulinum toxin type A injections in children with spastic forms of cerebral palsy].

We studied 67 children, aged 2-9 years, with cerebral palsy including 56 children with a spastic form. An electromyographic method was used for the development of optimal tactics of botulinum toxin type A injections in different clinical presentations of spasticity. The best clinical results were obtained in children with the following changes on EMG: 1) the tonic muscle activity in resting state was minimal (<10 microvolts) and had local or regional distribution; 2) the pathological synkinetic activity during voluntary movements was minimal (synergetic activity coefficient for shin muscles was less than 0.

[Hereditary thrombophilia in children: current views of etiology and pathogenesis].

This review is focused on the role of genetic factors in etiology and pathogenesis of thrombophilia in adults and children. Their knowledge permits to elucidate the main causes of this pathology and choose adequate measures for its prevention.

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms.

[Analysis of linkage and association of alleles of proinflammatory cytokines genes IL-6, IFNg and TNF with multiple sclerosis using transmission disequilibrium test (TDT)].

Proinflammatory cytokines Interleukin-6 (IL-6), Interferon-gamma (IFNg) and Tumor necrosis factor (TNF) are known as participants of inflammation and play an important role in pathogenesis of multiple sclerosis (MS). Based on literature data about influence of SNPs G(-308)A of TNF gene, A(+874)T of IFNG gene and G(-174)C of IL-6 gene on production of these cytokines, we investigated association of these polymorphic sites with MS. Linkage and association of alleles of these genes with MS was analyzed by transmission disequilibrium test (TDT).

[Effective treatment of multiple sclerosis with rebif-22 mcg in children and adolescences: results of a long-term study].

Management from an early age and availability of new treatment options have changed the outcome of paediatric patients with multiple sclerosis (MS). Currently available for treatment of MS in adults, such drugs as interferons beta and copolymer-1 are not widely used in paediatric neurological practice. The present long-term study of the effect of interferon beta la (rebif-22 mcg) included 20 children with MS from Moscow population.