Neurodevelopmental disorder associated with gene ARF3: A case report.

We present a case study of a patient exhibiting acquired microcephaly along with global developmental delay and drug-resistant epilepsy. Brain magnetic resonance imaging revealed distinctive features, including a Z-shaped morphology of the brainstem, volumetric reduction of white matter, diffuse thinning of the corpus callosum, and partial fusion of the cerebellar hemispheres at their most cranial portion. Whole-exome sequencing uncovered a pathogenic variant in the ARF3 gene c.200A>T, p.(Asp67Val). The neurodevelopmental disorder associated with the ARF3 gene is exceptionally rare, with only two previously documented cases in the literature. This disorder is characterized by global developmental delay and brain malformations, particularly affecting the white matter, cerebellum, and brainstem. It can also manifest as acquired microcephaly and epilepsy. These phenotypic characteristics align with Golgipathies, underscoring the significance of considering this group of conditions in relevant clinical contexts. In cases where a Z-shaped morphology of the brainstem is observed, ARF3-associated disorder should be included in the list of differential diagnoses.

Phenotypic/Genotypic Profile of Children with Neuronal Ceroid Lipofuscinosis in Southern Brazil.

INTRODUCTION: Neuronal ceroid lipofuscinoses (CLNs) are a group of lysosomal storage disorders of genetic origin, characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment. Thirteen genes related to CLNs are currently described, showing genetic and allelic heterogeneity, most of them with an autosomal recessive pattern. Due to the few descriptions of cases related to CLNs in Brazil, it is necessary to describe the phenotypic and genotypic characteristics of these patients. This study aims to evaluate the genotypic profile and correlate it with the phenotypic characteristics of patients with CLN in a children's hospital. METHODS: This study was performed as a descriptive cross-sectional study with analysis of medical records, imaging, and laboratory tests of patients who had a confirmed molecular diagnosis of CLN. RESULTS: The sample consisted of 11 patients from nine families with different subtypes of CLNs (CLN2, 5, 6, 7, and 8), with CLN2 being the most prevalent in the study. A total of 16 mutation variants were identified in genes associated with the five CLNs described in this study, with typical and atypical clinical phenotypes depending on the subtype and its variants. CONCLUSION: Novel mutations identified in the patients in this study showed phenotypes of rapid and severe progression in the CLN2 patient and similar characteristics in CLN6 and CLN7 patients, as previously described in the literature.

Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures.

OBJECTIVE: The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil. METHODS: A retrospective cross-sectional study was performed from January 2017 to December 2021. RESULTS: A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection. CONCLUSIONS: When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.

BRPF1-associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development.

In 2017, Mattiolli et al. and Yan et al. described a series of patients with clinical findings essentially characterized by intellectual disabilities, ptosis, hypotonia, epilepsy, and weakness. They also found in these patients distinct heterozygous mutations in the BRPF1 gene, which plays a role in epigenetic regulation by promoting histone acetylation. The disease is known as Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP, OMIM #617333). Later, another 20 patients were also described by distinct reports, suggesting IDDDFP could be a more frequent cause of intellectual disability as it was thought before. Here, we describe a patient with normal intellectual development who had congenital ptosis, hypotonia, muscular weakness, atlanto-axial malformation, and pyramidal at the neurological examination. The patient has a rare nonsense variant on exon 3 of BRPF1 gene. We also describe a phenotypic amplification for conditions related to deficiency in histone modifications.

Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features.

BACKGROUND: Mitochondria provide ATP through the process of oxidative phosphorylation, physically located in the inner mitochondrial membrane (IMM). The mitochondrial contact site and organising system (MICOS) complex is known as the 'mitoskeleton' due to its role in maintaining IMM architecture. APOO encodes MIC26, a component of MICOS, whose exact function in its maintenance or assembly has still not been completely elucidated. METHODS: We have studied a family in which the most affected subject presented progressive developmental delay, lactic acidosis, muscle weakness, hypotonia, weight loss, gastrointestinal and body temperature dysautonomia, repetitive infections, cognitive impairment and autistic behaviour. Other family members showed variable phenotype presentation. Whole exome sequencing was used to screen for pathological variants. Patient-derived skin fibroblasts were used to confirm the pathogenicity of the variant found in APOO. Knockout models in Drosophila melanogaster and Saccharomyces cerevisiae were employed to validate MIC26 involvement in MICOS assembly and mitochondrial function. RESULTS: A likely pathogenic c.350T>C transition was found in APOO predicting an I117T substitution in MIC26. The mutation caused impaired processing of the protein during import and faulty insertion into the IMM. This was associated with altered MICOS assembly and cristae junction disruption. The corresponding mutation in MIC26 or complete loss was associated with mitochondrial structural and functional deficiencies in yeast and D. melanogaster models. CONCLUSION: This is the first case of pathogenic mutation in APOO, causing altered MICOS assembly and neuromuscular impairment. MIC26 is involved in the assembly or stability of MICOS in humans, yeast and flies.

Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype-phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype-phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.

Addition of chickpea markedly increases the indigestible carbohydrate content in semolina pasta as eaten.

BACKGROUND: There is a growing interest in increasing dietary fiber (DF) consumption because of the health benefits associated with this nutrient. Pulses are considered a good source of non-digestible carbohydrates. The aim of this study was to investigate the possibility of substituting semolina with chickpea flour to increase indigestible carbohydrate content without altering the texture of the pasta. RESULTS: Pasta was prepared by extruding semolina-chickpea blends. The protein and DF content in the cooked pasta increased with the chickpea level, with an important contribution of resistant starch (RS) to the DF values. The optimum cooking time decreased as the chickpea content increased, which was related to the degree of starch gelatinization of the raw pasta. The in vitro digestible starch content decreased with the chickpea substitution level, concomitant with the increase in RS content. In general, the texture of the chickpea-containing pasta was similar to that of semolina pasta. CONCLUSIONS: Pending acceptability studies on these pastas may grant their promotion as good fiber sources, probably helpful in the fight against obesity and diet-related non-communicable diseases. © 2020 Society of Chemical Industry.

NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms.

Mitochondrial complex I (CI) deficiency is the most common oxidative phosphorylation disorder described. It shows a wide range of phenotypes with poor correlation within genotypes. Herein we expand the clinics and genetics of CI deficiency in the brazilian population by reporting three patients with pathogenic (c.640G>A, c.1268C>T, c.1207dupG) and likely pathogenic (c.766C>T) variants in the NDUFV1 gene. We show the mutation c.766C>T associated with a childhood onset phenotype of hypotonia, muscle weakness, psychomotor regression, lethargy, dysphagia, and strabismus. Additionally, this mutation was found to be associated with headaches and exercise intolerance in adulthood. We also review reported pathogenic variants in NDUFV1 highlighting the wide phenotypic heterogeneity in CI deficiency.

Enzyme Replacement Therapy Decreases Left Ventricular Mass Index in Patients with Hunter Syndrome?

Although enzyme replacement therapy (ERT) has shown benefit in improving cardiac systolic function in a murine model of cardiomyopathy associated with Hunter syndrome, few studies have analyzed its effect in humans. We evaluated the effect of ERT on patients with Hunter syndrome-related cardiomyopathy. We performed a retrospective analysis of serial transthoracic echocardiograms performed before and over the first 5 years after treatment initiation, in 14 patients with Hunter syndrome. An important cardiac remodeling occurred in all patients in this study. There was a significant reduction in left ventricular mass index from 70.88 to 26.75 g/m2.7 (p = 0.003), with a trend towards a decrease in relative wall thickness from 0.515 at baseline to 0.370 after 5 years of enzyme therapy (p = 0.140). No differences were observed in aortic root diameter, left atrial diameter, left ventricular diastolic and systolic diameters, left ventricular ejection fraction, or myocardial performance index. Our findings demonstrate that ERT contributes to reducing left ventricular mass index in patients with Hunter syndrome.

Clinical variability of children with anti-N-methyl-D-aspartate receptor encephalitis in southern Brazil: a cases series and review of the literature.

PURPOSE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease of the central nervous system (CNS). The aim of this study was to describe the variability of clinical presentation in anti-NMDAR encephalitis, treatment and outcomes in a case series of children and adolescents. METHODS: Retrospectively analyse patients diagnosed with anti-NMDAR encephalitis, from 2010 to 2018. RESULTS: The study population consisted of nine children with anti-NMDAR encephalitis from southern Brazil, six females and three males, aged 5 months to 16 years (mean 5 years). The time of follow-up varied between 1 and 7 years, with a mean of 3 years. The most frequent first manifestation consisted of seizures. All patients described had psychiatric symptoms and a wide spectrum of neurologic findings. Five patients had unilateral symptoms. Magnetic resonance imaging and electroencephalogram were normal in most patients. Cerebrospinal fluid pleocytosis occurred in five patients. All patients were administered immunoglobulin and/or steroids. Seven patients (78%) required cyclophosphamide and/or rituximab. Almost half of the patients fully recovered from all symptoms. CONCLUSIONS: A wide variety of symptoms were observed in this study and, although unilateral symptoms are rarely reported in the literature, a high frequency was observed among Brazilian children. Alternatives to first-line therapy should be considered in patients with clinical suspicion, even if they have not had a good response with first-line therapy.

Ice cream cone fortified with spent coffee ground: Chemical composition, quality and sensory characteristics, and in vitro starch digestibility.

The objective of the study was to evaluate the effect of the incorporation of spent coffee grounds in ice cream cones on the quality, sensory characteristics, and in vitro starch digestibility. The incorporation of spent coffee grounds in ice cream cones increased the content of dietary fiber and phenolic compounds. However, the quality and texture characteristics decreased with the addition of spent coffee grounds. The in vitro starch digestibility decreased significantly, resulting in a significant increase in resistant starch content. Fitting starch digestibility using the LOS-plot model revealed the presence of two sequential first-order digestion rates. Sensory analysis revealed that the panelists well accepted ice cream cones fortified with spent coffee grounds. The results suggest that spent coffee grounds are a potential ingredient for the formulation of food matrices with reduced starch digestibility, which contributes to the prevention of chronic degenerative diseases such as type II diabetes.

Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America.

BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America. METHODS: We analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately. RESULTS: Of the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five nontumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, nontumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient. CONCLUSIONS: OMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. Paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

Psychobehavioral factors and family functioning in mucopolysaccharidosis: preliminary studies.

Introduction: Mucopolysaccharidoses (MPS) constitute a group of progressive and multisystemic inherited metabolic diseases that profoundly affect both the mental health of patients and the wellbeing of their families. This study aims to evaluate the impact of MPS on family functioning and related factors. Methods and results: Twenty-five patients with MPS, including types I (n = 4), II (n = 11), IIIB (n = 2), IVA (n = 3), and VI (n = 5), and their families participated in this study. The mean patient age was 13 years [standard deviation (SD): 7.7 years]. Behavioral and emotional problems were noted in 9.1% of all patients. While the type of MPS did not directly influence mental problems, the presence of neuronal involvement did (p = 0.006). Patients with MPS III exhibited difficulties primarily in emotional areas, conduct, hyperactivity, and peer problems. Importantly, both patients with MPS II and those with MPS III experienced a significant impact on communication [mean scores for communication domain: MPS II, 35.6 (SD: 24.3); MPS III, 35.0 (SD: 22.6)]; poorer communication was directly linked to worse adaptive behavior (p = 0.012), and worse adaptive behavior was associated with lower quality of life (p = 0.001). Quality of life and caregiver burden among family members did not significantly differ across MPS types; however, higher caregiver burden was negatively associated with quality of life (p = 0.002). Concerning family functioning, the most impacted domains included independence, intellectual/cultural orientation, activity/recreation, and expressiveness. Domain scores did not vary based on MPS type, treatment, or neurological involvement. Quality-of-life scores were positively associated with the cultural/intellectual domain score. Conclusion: The impacts of quality of life and family extend beyond clinical characteristics and MPS type, strongly influenced by patient cognition and communication, as well as type of family functioning, especially those with greater cultural/intellectual skills of their family members. A multidisciplinary approach addressing the broader needs of individuals with MPS becomes essential. Techniques aimed at improving communication, including prompt interventions such as speech therapy and augmentative and alternative communication strategies, can contribute to overall family functioning improvement.

Brazilian consensus recommendations on the diagnosis and treatment of autoimmune encephalitis in the adult and pediatric populations.

BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.

Predictive factors of genetic diagnosis and real-life impact of next-generation sequencing for children with epilepsy.

OBJECTIVE: Identify the predictive variables of genetic pathogenic results and the impact of test results on epilepsy diagnosis and management. METHODS: Analytical observational design evaluated 130 patients with epilepsy that had performed genetic testing over January 2017 to July 2022. RESULTS: There was a gradual increase in the number of exams performed over the years. The frequency of pathogenic results was 34% (n = 44/130), 8 altered genes with 54% (n = 24/44) of the results. The tests were more positive in patients with developmental delay and/or regression (p = .01). None of the other factors analyzed were associated with higher diagnostic yield. The age at onset of epilepsy brought diagnostic yield to the test (p = .041). Patients with negative genetic test had a reduction in the number of electroencephalograms performed before and after the test (respectively, 3.80 ± 6.37 and .84 ± 1.67; p < .001). SIGNIFICANCE: Facing a large proportion of patients with unexplained epilepsy have a genetic cause a genetic test has the potential to reduce the use of unnecessary diagnostic tests, improve patient outcomes by identifying targeted treatments, and provide families with genetic counseling and risk assessment. But an early genetic testing can be crucial to reach these goals. Even in cases where the genetic test is negative, the study suggests that it still has important implications for patient care and management.

Neurological, neurobehavioral, and radiological alterations in patients with mucopolysaccharidosis III (Sanfilippo's syndrome) in Brazil.

Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is the most common form of MPS, in which neurological involvement in all stages of the disease is prominent. The current study aimed to comprehensively describe the neurological profile of children and adolescents with MPS III who visited the largest pediatric hospital in South America. A prospective/retrospective cohort analysis was performed on 10 patients with MPS III from eight unrelated families. Most patients <12 months of age had achieved development milestones within the expected range for their age, with delay in walking independently and first single word acquisition. Behavioral symptoms were reported in seven patients. Eight patients (80%) developed profound intellectual disabilities. Six patients (60%) had epilepsy, among whom 75% had their first seizure between 2 and 4 years of age; the frequency of which increased with age. Monotherapy was effective in 60% of patients. Two patients, both aged <8 years, had normal baseline electroencephalographic activity. Epileptiform activity was observed in three patients. Cortical atrophy was visualized using magnetic resonance imaging in 71% patients; all but one of these patients were aged >6 years. Neurological abnormalities increased in prevalence and severity with age. Anti-seizure drug resistance was uncommon. Dysmorphological and systemic manifestations were uncommon and mild and did not correlate with neurological involvement. Despite high allelic heterogeneity, neurodegeneration was similar among all patients. Overall, these data contribute to the scarce literature from developing countries.

GABAA receptor encephalitis associated with human parvovirus B19 virus infection: Case report.

RATIONALE: Human parvovirus B19 (B19) infection can produce a spectrum of clinical syndromes, including neurological manifestations, most notably encephalitis. Although symptoms suggestive of autoimmune disease in patients with B19 infection have been previously described, a clear association of autoimmune encephalitis with B19 infection has yet to be established. PATIENT CONCERNS: We describe the case of a 6-year-old boy who was hospitalized due to status epilepticus, which evolved to super-refractory status epilepticus that was only mildly responsive to anticonvulsant drugs. DIAGNOSIS: A cerebrospinal fluid study identified slight pleocytosis and B19 positivity. A subsequent autoimmunity cerebrospinal fluid study revealed the presence of anti-γ-aminobutyric acid type A (GABAA) receptor antibodies. INTERVENTIONS: After pulse therapy with methylprednisolone and continuous therapy with prednisolone with cyclosporine, the patient experiencing seizure persistence with disordered motor function manifestations and only minor improvement in consciousness, and so, plasmapheresis was performed. With continued immunosuppressive treatments with cyclosporine and prednisolone, the patient's clinical picture showed progressive improvement, with good control of seizures. Although the patient tolerated withdrawal of the anticonvulsant drugs well, he developed seizures when corticosteroid therapy withdrawal was attempted, so was started on azathioprine. OUTCOMES: After immunosuppressive therapy, the patient evolved with complete remission of symptoms, normal neurological examination and age-appropriate neuropsychomotor development. LESSONS: The present case characteristics, together with previous findings, support the hypothesis that autoimmunity may be triggered by extensive antigen release due to degeneration of infected neurons. This case highlights the importance of early clinical suspicion and treatment.

Neurological Characteristics of Pediatric Glycogen Storage Disease.

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.

Carbamazepine-Responsive Chorea in a Toddler with Semilobar Holoprosencephaly: Case Report.

Introduction: Holoprosencephaly (HPE) is a central nervous system malformation defined by incomplete separation of the prosencephalon in two hemispheres and determines a broad spectrum of clinical presentations based on extension of non-separation. Case Presentation: A 1 year and 8 months' old girl with semilobar HPE and 18p deletion syndrome was admitted to our hospital due to viral bronchiolitis. During hospitalization, she started generalized choreic movements, with face dyskinesia and without any identified aggravating factors. Haloperidol, clonazepam, and valproic acid did not achieve an attenuation of the movement disorder. Significant symptom relief was obtained with the use of trihexyphenidyl, with reduced amplitude and frequency of movements, but hyperthermia compromised its use. Control of chorea with no important side effects was only achieved after the introduction of carbamazepine. Discussion: Despite significant morbidity, there are few cases described in the literature of chorea and movement disorders in HPE and no effective treatment strategies described. Carbamazepine is an antiepileptic drug that stabilizes voltage-gated sodium channels and is the most effective treatment for paroxysmal kinesigenic dyskinesia. Although it has been used successfully in the treatment of different movement disorders, few therapeutic trials have been reported. The mechanism by which carbamazepine alleviates chorea is still unknown but may be justified through the blocking of post-synaptic dopamine receptors and stimulation of cholinergic pathways.

Effects of mixing, sheeting, and cooking on the starch, protein, and water structures of durum wheat semolina and chickpea flour pasta.

The influence of the pasta preparation stages on starch, proteins, and water structures of semolina and chickpea pasta was studied. The hydrated starch structures (995/1022 FTIR ratio) increased in semolina and reduced in chickpea pasta. The processing stages in semolina pasta led to a significant increase of ß-sheet structures (~50% to ~68%). The ß-sheet structures content in chickpea pasta was lower (~52%), and was most affected by sheeting and cooking. The water structure was assessed by the analysis of the OH fingerprint FTIR region (3700-2800 cm-1) and showing that water molecules (~90%) are strongly and moderately bound. The chickpea pasta displayed the highest content of strongly bonded water (about 55%) in contrast to the semolina pasta (~48%). A principal component analysis showed that the molecular organization of semolina pasta was mostly affected by dough formation and cooking; the molecular organization of chickpea pasta was determined by the cooking stage.