Polish recommendations for diagnosis and therapy of paediatric stroke.

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

Nusinersen treatment of Spinal Muscular Atrophy Type 1 - results of expanded access programme in Poland.

AIM OF THE STUDY: This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1. CLINICAL RATIONALE OF STUDY: Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. MATERIALS AND METHODS: We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18-26 months of treatment were compared to baseline. RESULTS: We analysed data from 26 patients with SMA type 1, mean age 4.79 (2-15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status.

Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation.

The HNRNPH2-associated disease (mental retardation, X-linked, syndromic, Bain type [MRXSB, MIM #300986]) is caused by de novo mutations in the X-linked HNRNPH2 gene. MRXSB has been described in six female patients with dysmorphy, developmental delay, intellectual disability, autism, hypotonia and seizures. The reported HNRNPH2 mutations were clustered in the small domain encoding nuclear localization signal; in particular, the p.Arg206Trp was found in four independent de novo events. HNRNPH1 is a conserved autosomal paralogue of HNRNPH2 with a similar function in regulation of pre-mRNAs splicing but so far it has not been associated with human disease. We describe a boy with a disease similar to MRXSB in whom a novel de novo mutation c.616C>T (p.Arg206Trp) in HNRNPH1 was found (ie, the exact paralogue of the recurrent HNRNPH2 mutation). We propose that defective function of HNRNPH2 and HNRNPH1 nuclear localization signal has similar clinical consequences. An important difference between the two diseases is that the HNRNPH1-associated syndrome may occur in boys (as in the case of our proband) which is well explained by the autosomal (chr5q35.3) rather than X-linked localization of the HNRNPH2 gene.

Mathematical evaluation of melatonin secretion in hypoxic ischemic encephalopathy.

OBJECTIVES: The aims of the study were to assess the kinematics of the lower limbs and pelvis during normal walking in professional ballet dancers and to investigate relationships between movements of segments of the lower limbs and pelvis. METHODS: Thirty one professional ballet dancers and twenty eight controls completed five walking trials at their preferred speed. Kinematic data in the basic anatomical planes for ankle, knee, and hip joints as well as for the pelvis were collected with an optoelectronic motion system. RESULTS: The female ballet dancers had in comparison with the controls significantly larger (p < 0.01) knee flexion in the swing phase and hip abduction in the preswing phase. Compared to the control group, the male ballet dancers had significantly larger dorsiflexion in the final stance and the total pelvic tilt range of motion. The number of significant correlations between kinematic parameters was higher in the female ballet dancers. CONCLUSIONS: It can be concluded that specific movement techniques and compensatory strategies used in ballet dance can alter relationships between movements of segments of the lower limbs during normal walking. The relationships between movements in the joints of the lower limbs and pelvis are stronger in women.

Upstream Stimulating Factor 1 (USF-1) Gene Polymorphisms and the Risk, Symptoms, and Outcome of Pediatric Ischemic Stroke.

BACKGROUND: Pediatric ischemic stroke is an important cause of morbidity and mortality. As previous studies of children after stroke showed, dyslipidemias were very common in Polish and other European populations. Thus, looking for genetic factors predisposing to pediatric stroke, its symptoms, and outcome, we have analyzed 2 polymorphisms of the upstream stimulating factor 1 (USF-1) gene. MATERIALS AND METHODS: The study group consisted of 82 children with stroke, 156 parents, and 146 controls. We used 2 alternative methods: the case-control model and the analysis of families using the transmission disequilibrium test. The 2 polymorphisms, rs2516839 and rs3737787, were genotyped using the TaqMan Pre-Designed SNP Genotyping Assay. The Statistica 10.0 software was used in all statistical analyses. RESULTS: We did not observe any statistical differences in genotype and allele frequencies between patients and controls. There were also no significant differences in the transmission of alleles from the parents to the affected children. However, we have observed that the TT genotype of the rs2516839 polymorphism was more common in patients with epilepsy and dysarthria, whereas the TT genotype of the rs3737787 polymorphism was more frequent in the group of patients with a decrease in intellectual functioning. CONCLUSIONS: Our study did not show any associations between the 2 analyzed polymorphisms of the USF-1 gene and pediatric ischemic stroke. However, we have observed an influence of specific genotypes on the outcome of stroke, including epilepsy, dysarthria, and a decrease in intellectual functioning.

The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study.

BACKGROUND: The association of 9p21.3 locus single nucleotide polymorphisms with arterial ischemic stroke in adults was demonstrated in many studies, but there are no studies in pediatric arterial ischemic stroke patients. We investigated whether the 9p21.3 locus polymorphism, namely rs10757278, is associated with the arterial ischemic stroke risk in children. METHODS: The study group consisted of 335 individuals: 80 children with arterial ischemic stroke, their biological parents (n = 122), and 133 children (age and sex matched) without any symptoms of arterial ischemic stroke as a control group. The rs10757278 polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). Two different study design models were used: family-based association test (transmission-disequilibrium test) and case-control model. RESULTS: There were no statistically significant differences in the distribution of genotypes and alleles of the rs10757278 polymorphism between groups of children with arterial ischemic stroke and controls. The frequency of both transmitted alleles in transmission-disequilibrium test analysis was identical (50%). The A allele carrier state (AA+AG genotype) was more frequent in arterial ischemic stroke children with hemiparesis than in patients without this symptom (94.5% versus 68.0%, P = .004). CONCLUSIONS: There is no evidence to consider the 9p21.3 locus polymorphism as a risk factor for childhood arterial ischemic stroke.

Methylenetetrahydrofolate reductase gene A1298C polymorphism in pediatric stroke--case-control and family-based study.

Moderate hyperhomocysteinemia is one of the risk factors of pediatric stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme, which regulates homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are associated with a decreased activity of the enzyme. The aim of the study was to assess an association between the A1298C polymorphism and pediatric stroke. We also evaluated a possible synergistic effect of A1298C and C677T polymorphisms of this gene. The study group consisted of 88 children after ischemic stroke, 142 of their parents and 111 controls. The A1298C polymorphism was genotyped using the restriction fragment length polymorphism method. We used 2 study designs: a case-control model and a family-based association test. The Statistica 7.1 and EpiInfo 6 softwares were used in all analyses. We did not observe any statistically significant differences either in the transmission of the A allele in the family-based test or in the frequency of the A allele in the patients group compared with the controls. We also did not notice any significant additive or synergistic effects between the A1298C and C677T polymorphisms. An analysis of the results obtained in this study and a critical review of previously published studies indicate that the A1298C polymorphism of the MTHFR gene is not related to ischemic stroke in children.

Polymorphism of ABCB1/MDR1 C3435T in children and adolescents with partial epilepsy is due to different criteria for drug resistance - preliminary results.

BACKGROUND: The diagnosis of "drug resistance" in epilepsy can be defined and interpreted in various ways. This may be due to discrepant definitions of drug resistance to pharmacotherapy. The aim of our study was to investigate the relationship between C3435T polymorphism of the MDR1 gene and drug resistance in epilepsy with the consideration of 4 different criteria for qualification to groups sensitive and resistant to applied pharmacotherapy. MATERIAL AND METHODS: Evaluation of C3435T polymorphism of MDR1/ABCB1 gene was conducted on a group of 82 white children and young adolescents up to 18 years old. While qualifying the patients to the group of sensitive or drug resistant, the following 4 definitions of drug resistance were applied: the ILAE's, Appleton's, Siddiqui's, and Berg's. RESULTS: A detailed analysis of genotypes of the MDR1 gene did not show any significant discrepancies between the groups of patients resistant and sensitive to antiepileptic drugs (AEDs) in 4 consecutive comparisons taking into consideration various criteria of sensitivity and resistance to pharmacotherapy. CONCLUSIONS: The obtained results clearly confirm the lack of a connection between the occurrence of drug-resistant epilepsy and C435T polymorphism of the MDR1 gene irrespective of the definition of drug resistance applied to the patient.

Postural control before and after transitional locomotor tasks in children on the autism spectrum: A case-control study.

BACKGROUND: Instrumented measurements of postural control provide a more accurate insight into the motor development of children with autism. This study aimed to identify postural control deficits in autistic children during quiet standing before and after transient locomotor task. It was hypothesized that the parameters that characterize the trajectory of center of foot pressure (COP) displacement would be higher in autistic children compared to typically developing children. METHODS: Sixteen autistic children aged 6-10 but without a comorbidity diagnosis, were enrolled in the study group. The control group comprised 16 typically developing peers. The assessment of the transitional task comprised four different conditions: unperturbed and perturbed transition, stepping up, and stepping down tasks. Analysis of the COP signal was carried out for three distinct phases, i.e., phase 1 - quiet standing before step initiation, phase 2 - transit, and phase 3 - quiet standing until measurement completion. FINDINGS: The two-way ANOVA with a 2 × 4 factorial design (group × testing condition) revealed a group effect on all posturographic variables in the antero-posterior and medio-lateral directions of phase 1 and in the antero-posterior direction of phase 3. The Bonferroni post-hoc test showed the means of all those variables were significantly higher for the autistic than for typically developing children. Group allocation also had an effect on the time of transit and step length, which turned out to be significantly longer in autistic children compared to healthy peers. INTERPRETATION: Autistic children show increased postural sway before and after transitional locomotor tasks compared to typically developing children. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12621001113842; date registered: 23.08.2021).

Modulation of center-of-pressure signal in children on the autism spectrum: A case-control study.

BACKGROUND: Proper postural and motor control plays a fundamental role in the child's ontogenetic development. So far, the postural control in children on the autism spectrum has mainly been assessed with standard posturographic measurements of center of pressure (COP) displacements. RESEARCH QUESTION: What are the differences in postural control between autistic and typically developing children? METHODS: The study group comprised 16 autistic children aged 6-10 years, identified by a psychiatrist. The control group consisted of 16 typically developing children aged 6-10 years with no posture deformities, no pervasive developmental disorder and no history of postural control or movement deficits. The data were collected during quiet standing with eyes open using a force plate. To gain a better insight into the postural control processes, the rambling-trembling and sample entropy analyses were used in COP data processing. RESULTS: Compared to typically developing children, those with autism spectrum had significantly higher values of COP and rambling trajectory parameters in the antero-posterior direction during quiet standing. The variables of the trembling trajectory did not differ significantly between the groups. The autistic children had significantly lower values of sample entropy in the antero-posterior direction compared to typically developing children. SIGNIFICANCE: More advanced measures of COP displacements including the rambling-trembling method and sample entropy revealed differences in postural control between autistic and typically developing children. These methods may therefore contribute to functional assessment of postural control deficits in children on the autism spectrum.

Expanding the Knowledge of KIF1A-Dependent Disorders to a Group of Polish Patients.

BACKGROUND: KIF1A (kinesin family member 1A)-related disorders encompass a variety of diseases. KIF1A variants are responsible for autosomal recessive and dominant spastic paraplegia 30 (SPG, OMIM610357), autosomal recessive hereditary sensory and autonomic neuropathy type 2 (HSN2C, OMIM614213), and autosomal dominant neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment (NESCAV syndrome), formerly named mental retardation type 9 (MRD9) (OMIM614255). KIF1A variants have also been occasionally linked with progressive encephalopathy with brain atrophy, progressive neurodegeneration, PEHO-like syndrome (progressive encephalopathy with edema, hypsarrhythmia, optic atrophy), and Rett-like syndrome. MATERIALS AND METHODS: The first Polish patients with confirmed heterozygous pathogenic and potentially pathogenic KIF1A variants were analyzed. All the patients were of Caucasian origin. Five patients were females, and four were males (female-to-male ratio = 1.25). The age of onset of the disease ranged from 6 weeks to 2 years. RESULTS: Exome sequencing identified three novel variants. Variant c.442G>A was described in the ClinVar database as likely pathogenic. The other two novel variants, c.609G>C; p.(Arg203Ser) and c.218T>G, p.(Val73Gly), were not recorded in ClinVar. CONCLUSIONS: The authors underlined the difficulties in classifying particular syndromes due to non-specific and overlapping signs and symptoms, sometimes observed only temporarily.

The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls.

The 677C>T polymorphism within methylenetetrahydrofolate reductase (MTHFR) gene is related to an elevated level of homocysteine. Thus it may be considered as a genetic risk factor in ischemic stroke. Apparently studies of this type of polymorphism in childhood stroke have shown conflicting results. We performed meta-analysis of all the data that are available in relation with MTHFR polymorphism and the risk of ischemic stroke in children. We searched PubMed (last search dated December 2010) using "MTHFR polymorphism", "ischemic stroke" "child", "children", "pediatric stroke" as keywords and reference lists of studies and reviews on the topic. Finally, 15 case-control studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 822 children and adolescents after ischemic stroke and 1,552 control subjects. Fixed or random effects models were used depending on the heterogeneity between the studies. The association between ischemic stroke and 677C>T polymorphism within MTHFR gene was observed in three of the studies. The pooled analysis showed that TT genotype of MTHFR gene is more common in stroke patients than in controls (p = 0.0402, odds ratio = 1.57, 95 % confidence interval 1.02-2.41). The Egger's test did not reveal presence of a publication bias. The results based on a sizeable group of cases and controls have proved that the 677C>T polymorphism in MTHFR gene is associated with the development of ischemic stroke in children.

A Dialogue in the Medical Perspective-Body Mass and Nutritional Status Disorders during the Development Period.

Eating disorders among children and youth are a serious social problem. The time of development is the starting point in shaping eating patterns. Proper nutrition provides the basis for psychophysical development. A knowledgeable pediatrician can improve society's health by engaging parents and, later, the child or youth. We offer knowledge on the nutrition basics and the commonly available tools to assess the nutritional status. We will discuss the characteristics of eating and body mass disorders in developing children. We will provide information on the warning signals of eating and body mass disorders and recommend prophylaxis. The reader will be familiarized with the motivational dialogue as an effective control tool for the discussed health issues.

Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.

The aim of the study was to perform family-based association analysis of PRKCB1, CBLN1 and KCNMB4 gene polymorphisms and autism disorder. We comprised 206 Caucasian children with autistic spectrum disorder (ASD) and their biological parents. In transmission/disequilibrium test we observed that T-allele of the rs198198 polymorphism of the PRKCB1 gene was more often transmitted to affected children in the male subgroup (p = 0.010). Additionally, the T carrier state was significantly associated with hypotonia (p = 0.048). In the female subgroup, the T-allele carriers more often showed more mobile/vital behavior (p = 0.046). In conclusion, our study showed that the rs198198 of the PRKCB1 gene may be associated with ASD in men and with some features characteristic for the disorder.

Pediatric-onset multiple sclerosis in Poland: A registry-based retrospective cohort study.

BACKGROUND: Epidemiologic data on pediatric-onset multiple sclerosis (POMS) in Central and Eastern Europe are limited. The aim of this study was to determine the incidence, prevalence and the clinical features of POMS in Poland. METHODS: Registry-based retrospective study was conducted among Polish children population (age ≤ 18 years), between 1 January 2010 and 31 December 2019. A total of 329 pediatric or juvenile patients fulfilled the International Pediatric MS Study Group (IPMSSG) criteria for MS, reported to the Polish Multiple Sclerosis Registry, were considered for estimation of age- and sex-specific prevalence (per 100,000 persons), and incidence rates (per 100,000 person-years). The demographic data, clinical presentation and treatment strategies also were investigated. RESULTS: On December 31, 2019 in the database were collected data of 329 patients up to 18 years with POMS diagnosis (101 boys and 228 girls; mean age 15.3 ± 3.8 years). The age-adjusted prevalence standardized to the European Standard Population was 5.19/100,000 (95% confidence interval (CI), 4.64-5.78). A significantly higher prevalence was recorded in girls (7.41; 95% CI, 6.48-8.44) than in boys (3.08; 95% CI, 2.50-3.74; P<0.001). The mean annual standardized incidence in Poland between 2015 - 2019 was 0.77 (95%CI, 0.45-1.02) per 100,000 person-years. The highest overall standardized incidence 1.06 (95%CI, 0.82-1.34) was noted in 2018. Most of patients (95.7%) had relapsing-remitting disease with polysymptomatic onset in one-thirds of the cases, and 82.3% were treated with disease-modifying drugs. Family history of MS was reported in 26 cases (7.9%). CONCLUSION: In this first report of registry-based study from Poland an increasing prevalence and incidence of POMS was found during the last years. This temporal trend corroborate the findings of studies conducted elsewhere.

The Clinical and Epidemiological Profile of Paediatric-Onset Multiple Sclerosis in Poland.

Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing−remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64−5.78). Significantly higher prevalence was noted in the 13−18 years group (7.12; 95% CI, 6.64−7.86) than in the 9−12 years group (3.41; 95% CI, 2.98−3.86) and the <9 years group (0.56; 95% CI, 0.46−0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender.

Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder-A Systematic Review.

Autism spectrum disorder (ASD) and cerebral palsy (CP) are some of the most common neurodevelopmental diseases. They have multifactorial origin, which means that each case may manifest differently from the others. In patients with ASD, symptoms associated with deficits in social communication and characteristic, repetitive types of behaviors or interests are predominant, while in patients with CP, motor disability is diagnosed with accompanying cognitive impairment of various degrees. In order to minimize their adverse effects, it is necessary to promptly diagnose and incorporate appropriate management, which can significantly improve patient quality of life. One of the therapeutic possibilities is stem cell therapy, already known from other branches of medicine, with high hopes for safe and effective treatment of these diseases. Undoubtedly, in the future we will have to face the challenges that will arise due to the still existing gaps in knowledge and the heterogeneity of this group of patients. The purpose of this systematic review is to summarize briefly the latest achievements and advances in stem cell therapy for ASD and CP.

Dravet Syndrome-The Polish Family's Perspective Study.

AIM: The aim of the paper is to study the prevalence of Dravet Syndrome (DS) in the Polish population and indicate different factors other than seizures reducing the quality of life in such patients. METHOD: A survey was conducted among caregivers of patients with DS by the members of the Polish support group of the Association for People with Severe Refractory Epilepsy DRAVET.PL. It included their experience of the diagnosis, seizures, and treatment-related adverse effects. The caregivers also completed the PedsQL survey, which showed the most important problems. The survey received 55 responses from caregivers of patients with DS (aged 2-25 years). RESULTS: Prior to the diagnosis of DS, 85% of patients presented with status epilepticus lasting more than 30 min, and the frequency of seizures (mostly tonic-clonic or hemiconvulsions) ranged from 2 per week to hundreds per day. After the diagnosis of DS, patients remained on polytherapy (drugs recommended in DS). Before diagnosis, some of them had been on sodium channel blockers. Most patients experienced many adverse effects, including aggression and loss of appetite. The frequency of adverse effects was related to the number of drugs used in this therapy, which had an impact on the results of the PedsQL form, particularly in terms of the physical and social spheres. Intensive care unit stays due to severe status epilepticus also had an influence on the results of the PedsQL form. CONCLUSIONS: Families must be counseled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns, sleep abnormalities). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work.

The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant.

BACKGROUND: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in ALG13, characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients. METHODS: Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients. RESULTS: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. CONCLUSIONS: Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance.

Eating Behaviors of Children with Autism-Pilot Study.

Autism Spectrum Disorder (ASD) is the most recognized neuropsychiatric disorder of childhood. Comorbid conditions (such as feeding disorders) are more common among people with autism than among the general population. The most frequent somatic disorders in autistic children include the gastrointestinal disorders observed in 46-91% of patients. The purpose of this study was the evaluation of the nutrition of children with autism, with particular emphasis placed on feeding in the first year of life, in comparison to the group of healthy peers. Participants included 75 Caucasian children (41 children diagnosed with pure autism, and the control group consisting of 34 children without autistic traits). The analysis was performed based on a questionnaire of own design with the first part devoted to the eating practices of the early infancy. Results: Autistic children, as compared to the healthy peers, presented a shortened time of breastfeeding (the children fell asleep at the breast) (p = 0.04), a delayed introduction of dairy products (p = 0.001), the need of more trials to introduce new foods (p = 0.006), a delayed introduction of foods with solid and lumpy structure (p = 0.004), a longer duration of bottle feeding (p = 0.005), delayed attempts to eating using own hands (p = 0.006) and needed a greater support of parents to divert their attention from food during eating (p = 0.05). Conclusions: 1. The dietary problems are more common among children with the autism spectrum disorder than among the population of healthy children, during the first year of life from the time of introducing the complementary foods. 2. The autistic children experience difficulties with eating and require their parents' additional involvement significantly more often than their healthy peers.