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 (
c.247C>T and c.1039C>T). Six previously unreported variants were identified (5
; 1
). 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
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.
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.
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.
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.
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.
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.
Knowledge of the genes affecting maize ear inflorescence may lead to better grain yield modeling. Maize ear fasciation, defined as abnormal flattened ears with high kernel row number, is a ...quantitative trait widely present in Portuguese maize landraces.
Using a segregating population derived from an ear fasciation contrasting cross (consisting of 149 F2:3 families) we established a two location field trial using a complete randomized block design. Correlations and heritabilities for several ear fasciation-related traits and yield were determined. Quantitative Trait Loci (QTL) involved in the inheritance of those traits were identified and candidate genes for these QTL proposed.
Ear fasciation broad-sense heritability was 0.73. Highly significant correlations were found between ear fasciation and some ear and cob diameters and row number traits. For the 23 yield and ear fasciation-related traits, 65 QTL were identified, out of which 11 were detected in both environments, while for the three principal components, five to six QTL were detected per environment. Detected QTL were distributed across 17 genomic regions and explained individually, 8.7% to 22.4% of the individual traits or principal components phenotypic variance. Several candidate genes for these QTL regions were proposed, such as bearded-ear1, branched silkless1, compact plant1, ramosa2, ramosa3, tasselseed4 and terminal ear1. However, many QTL mapped to regions without known candidate genes, indicating potential chromosomal regions not yet targeted for maize ear traits selection.
Portuguese maize germplasm represents a valuable source of genes or allelic variants for yield improvement and elucidation of the genetic basis of ear fasciation traits. Future studies should focus on fine mapping of the identified genomic regions with the aim of map-based cloning.
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.
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.
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.
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.
After immunosuppressive therapy, the patient evolved with complete remission of symptoms, normal neurological examination and age-appropriate neuropsychomotor development.
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.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease that induces a wide spectrum of symptoms, especially in toddlers. These include acute-onset movement disorders, ...with neurological regression, and other associated neurological symptoms. Anti-NMDAR encephalitis remains a diagnostic challenge, especially in toddlers, with better prognosis associated with early treatment. We report the case of a 15-months-old boy who initially presented with vomiting and later with acute-onset dystonia after the administration of antiemetics. Within 14 days, the patient developed neuropsychomotor developmental regression and worsening dystonia. After ruling out an acute dystonic reaction and glutaric acidemia type 1 (GA-1), a final diagnosis of anti-NMDAR encephalitis was made. The patient responded well to immunomodulatory therapy. The present case underscores the importance of early treatment for patient prognosis and of including anti-NMDAR encephalitis in the differential diagnosis of acute-onset movement disorders.
Respiratory muscle strength (RMS) is a determinant of vital capacity, and its decline can lead to inadequate ventilation and deficiency in the elimination of secretions from the airways. Studies ...analyzing RMS in older adults with Parkinson's disease (PD) and Alzheimer's disease (AD) remain scarce, making the analysis of this variable still very uncertain. The aim of this study was to analyze the RMS of older adults diagnosed with PD and AD, in relation to healthy control peers.
A cross-sectional study was conducted involving 65 older adults comprising 3 groups: PD (n = 20), AD (n = 20), and control (n = 25). The participants underwent anthropometric and cirtometric measurements associated with maximal respiratory pressures. We analyzed data using descriptive (mean and SD) and inferential statistics (1-way analysis of variance, Student t test, and Scheffé post hoc) with a level of significance of 5% (P < .05) and a CI of 95%.
Although the anthropometric and cirtometric variables indicated similarity of values between groups (P > .05), the maximal inspiratory and expiratory pressures were considerably lower in the subjects with PD and AD (P < .01).
The control of the anthropometric and cirtometric variables of the subjects indicates that RMS is affected by the aging process, and its decline increases in neurodegenerative conditions. This fact represents a serious risk for the development of atelectasis and other pneumo-functional complications, which must be considered in proposing of future therapies.
In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles ...(SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.
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•Cit_SPIONs preferentially accumulate in Leydig cells after testicular injection.•Within 56 days, Cit_SPIONs spread across all testis parenchyma.•Cit_SPIONs significantly reduce steroidogenic activity in mouse Leydig cells.•Cit_SPIONs maintain spermatogenesis pace but lower daily sperm production.
This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single ...center in Brazil.
This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann–Whitney U or chi-square tests.
Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174–0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p<0.001.
Children with infantile epileptic spasms syndrome have a higher risk of being diagnosed with autism spectrum disorder. Later age of onset and period of spasm occurrence might be predisposing risk factors.
To expand the clinical phenotype of
mutations by assessing the functional consequences of a missense and a splicing acceptor mutation.
We performed whole-exome sequencing for identification of likely ...pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by
H-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts.
The patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and the splicing region c.1771-6C>G mutation in
, the gene coding for the catalytic subunit of RNA polymerase III (Pol III). Aberrant splicing was observed for the c.1771-6C>G mutation. Decreased RNA expression levels of Pol III targets (HNRNPH2, ubiquitin B, lactotransferrin, and HSP90AA1) were observed in patient fibroblasts with rescue to normal levels by overexpression of the wild-type protein but not by the p.Val1241Met variant.
Mutations in the
gene cause
-related hypomyelinating leukodystrophy with or without oligodontia or hypogonadotropic hypogonadism (HLD7, OMIM: 607694) and neonatal progeroid syndrome (OMIM: 264090), both with high phenotypic variability. We demonstrated the pathogenicity of c.1771-6C>G and c.3721G>A mutations causing an early-onset disorder. The phenotype of our patient expands the clinical presentation of
-related mutations and suggests a new classification that we propose designating as Neurodevelopmental Disorder with Regression, Abnormal Movements, and Increased Lactate.
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