Larissa Baccoli de Souza

*Correspondence: marq.lari@gmail.com. Abstract Background: Chronic exposure to stressful stimuli can result in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased circulating cortisol levels. When this dysregulation occurs during early stages of life, including during pregnancy, it can affect cognitive development and increase the risk of depression and anxiety disorders throughout life. There is evidence that mothers who have experienced traumatic situations before conception, during pregnancy, or in the early months of their offspring's life exhibit alterations in salivary cortisol levels and so do their infants, even if they have not directly experienced the stressful stimuli. Objective: To investigate whether there are effects of maternal cortisol levels and/or infant cortisol levels on total brain volume (TBV) and head circumference (HC) of infants (at birth and on the day of magnetic resonance imaging) in the first month of life. Methods: A multivariate generalized linear model (GLM) was conducted to investigate the effects of maternal cortisol levels and infant cortisol levels on TBV obtained from magnetic resonance imaging and HC of infants from a cohort in São Paul, comprising mothers with and without a history of childhood maltreatment (case and control group). GLM analysis was conducted separately by sex and controlled for group and infant age in weeks on the day of MRI, referenced from the mother's last menstrual period before gestation (PMA). The statistical significance was set at 0.016 (i.e., 0.05/3; Bonferroni correction). Results: Data from 126 dyads (F=57) were analyzed. The mean PMA of infants was 43.7 (±1,64) days. GLM showed a trend of maternal cortisol effect on HC obtained on the day of MRI only in female infants (F(1)=4.351; p=0.042; η²=0.077), suggesting that higher maternal cortisol levels were associated with smaller HC in female infants on the day of MRI (β=-0,78; t=-2,086). Conclusion: The analyses showed lack of evidence for the impact of cortisol levels (maternal and infant) on TBV and HC at birth in the overall sample and in the group of male infants. However, a trend was observed for maternal cortisol to predict HC of female infants on the day of MRI (PMA=47.7days), where higher maternal cortisol levels were associated with smaller HC, suggesting a negative impact of stressful events during pregnancy on neurodevelopment. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: andreasayurimurata@gmail.com. Abstract Case Presentation: L.E.S.P., 10 years-old, male, was referred to our service due to muscle weaknnes in the lower limbs 1 week ago, associated with daily vomiting with weight loss of 6 kg in 1 month. On examination, he has grade IV muscle strength and hyporreflexia in lower limbs, hip tilt, positive gowers signal, and no other changes. History of a similar condition 3 months ago with spontaneous resolution. Performed initial tests with creatine kinase (CK) 15173, lactic dehydrogenase (LD) 16600, glutamic pyruvic transaminase (GPT) 750 and glutamic oxaloacetic transaminase (GOT) 1915; magnetic resonance imaging (MRI), without alterations; electroneuromyography with a decrease in the amplitude of motor unit powers and abdominal ultrasound showing mild hepatic steatosis (grade I). Collected panel for neuromuscular disease research, positive for multiple acyl-coenzyme A dehydrogenase deficiency (MADD) or glutaric academia IIC. After 1 month the patient evolved with clinical improvement. Presenting no new events after the introduction of riboflavin. Discussion: Deficiency of multiple acyl-CoA dehydrogenases (MADD) or glutaric acidemia IIC has an autosomal recessive inheritance and can present in 3 ways according to the gene involved. Neonatal form with congenital anomalies (type I), usually manifests with severe non-ketotic hypoglycemia, hypotonia, hepatomegaly and metabolic acidosis in the first 24 hours of life and usually evolves to death in the first week of life. Neonatal form without congenital anomalies (type II), presents onset in the first 24 to 48 hours of life with symptoms similar to type I. Mild form or late presentation (type III), manifests with chronic myopathy (intolerance to physical exercise, weakness muscular pain, myalgia), metabolic acidosis, hypoglycemia, increase in transaminases and elevation of muscle enzymes after decompensation. In addition to the different clinical forms, some features may be present, such as dysplastic or polycystic kidneys, blotter foot, hypertelorism, high forehead, low-set ears, wide anterior fontanelle, sweaty foot odor, anomalies in the external genitalia and midline hypoplasia from the face. The diagnosis is made through molecular analysis. Although there is no curative treatment, it is known that patients respond satisfactorily to the use of riboflavin. Final Comments: In view of this situation, reaffirms itself the importance of suspecting inborn errors of metabolism in recurrent conditions that can be triggered by an infectious or metabolic condition Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: lahdecarvalho@gmail.com. Abstract Background: The Chikungunya disease is an arboviral infection caused by an alphavirus. The disease was first reported in the 1960’s, but major outbreaks became more evident on the tropics in early 2000’s. Systemic and neurological complications are being increasingly recognized since then. Objective: To report two different Central Nervous System (CNS) manifestations of the chikungunya virus (CHIKV) in the early infancy and neonatal period. Methods: The patients were clinically evaluated and had imaging, laboratorial and serology studies performed. Results: Case 1 – Five-month-old female patient, living on the rural district of a northern Minas Gerais city, first presented with high fever and inconsolable crying. She developed bullous and erythematous skin lesions on the third day. As the disease progressed, pancytopenia, hepatic and renal disfunction became more evident. At this point, dialyses was prescribed. Alongside with ionic instability and systemic disfunctions, the patient presented with Status epilepticus, resolved after a 10mg/kg phenobarbital attack. Head computed tomography presented with cortical atrophy. Cerebrospinal fluid (CSF) analyzes showed no signs of inflammation and was negative for CHIKV. CHIKV disease was confirmed through serology exams which demonstrated high IgM serum levels. Case 2 – Female term newborn, born in Belo Horizonte, presenting with sepsis-like symptoms (respiratory distress) on the first day of life. The mom had a history of fever and erythematous lesions during childbirth. The patient evolved with cardiac arrhythmia, feeding intolerance, glycemic instability and bullous skin lesions. Neonatal seizures controlled with 20mg/kg phenobarbital attack. Transfontanelle ultrasound revealed subependymal hemorrhage on the left side and CSF studies had an inflammation pattern with elevated protein (847mg/dL). CHIKV vertical infection was confirmed through newborn and mother positive serum RT-PCR studies. Conclusion: CHIKV infection became a common viral disease in South America on the last few years. Hence, knowledge of the various systemic and neurological symptoms is essential for optimal recognition and for guiding the treatment plan. This series of cases shows two pediatric patients, from different age groups. The former fulfilling criteria for CHIKV encephalopathy (Case 1) and the latter (Case 2) the CHIKV encephalitis. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: matheus_bh09@hotmail.com. Abstract Case Presentation: Case 1: A male child had normal neurological development until one year old. Then, he started having episodes of vomit and diarrhea, followed by hypoglycemia and seizures. These events were followed by regression in his development, cognitive decline and progressive spastic tetraparesis. During the investigation, he was also diagnosed with hypothyroidism and epilepsy. Brain magnetic resonance imaging (MRI) had diffused cerebral and cerebellar atrophy, along with a thin corpus callosum. Whole exome sequencing (WES) showed a pathogenic variant in TANGO2, which allowed the diagnosis of TANGO2 deficiency. Case 2: During the investigation of patient of case one, the younger sister presented a similar story. Normal development until 15 months old, when the first metabolic crisis occurred. Patient needed support of the pediatric intensive care unit (PICU) and intubation. Afterwards, she developed epilepsy, hypotonia, gait impairment and development regression. Further genetic investigation showed the same pathogenic variant in TANGO2 as in her brother. Discussion: Pathogenic variants in TANGO2 (Transport and Golgi Organizations 2 Homolog) were first identified in 2016. Patients present with global developmental delay, ataxia, epilepsy, progressive cognitive decline, encephalopathy, hypothyroidism and life-threatening metabolic crisis with hypoglycemia, rhabdomyolysis, cardiac arrhythmias and cardiomyopathy. Symptoms usually start in infancy and developmental delay is often the first sign. It is an autosomal recessive condition and the diagnosis of patients with suggestive phenotype occurs by the identification of biallelic pathogenic variants in TANGO2. Also, in metabolic crisis, elevated creatine phosphokinase (CPK) and liver enzymes, along with hypoglycemia, lactic acidosis, mild hyperammonemia and QTc prolongation can be found. Imaging shows diffuse atrophy, ventriculomegaly and diminished white matter. There is no specific treatment. Daily supplementation of B Complex vitamins is indicated, along with antiepileptic drug therapy (AED), levothyroxine as needed, rehabilitation therapies and psychological support for patients and caregivers. During the acute metabolic crisis, support care is needed to acknowledge the complications, such as hypoglycemia, arrhythmias and rhabdomyolysis. Final Comments: TANGO2 deficiency is a rare condition with poor prognosis. However, knowing this disorder is important in order to prevent recurrent crises and improve patients’ and caregivers’ quality of life. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: claracpinhati@hotmail.com. Abstract Case Presentation: We present the case of a female patient, healthy until 6 months old, when she presented a first episode of hypotonia and weakness in lower members that occurred 3 days after pentavalent and inactivated polio vaccination. The symptoms lasted 7 days and were followed by progressive improvement without any treatment, but she remained with distal motor deficit. Later, she presented two other episodes of muscle weakness, the first at 1 year old, that occurred 7 days after triple viral and pneumococcal vaccination, and the second at 2 years and 8 months old, after a bug bite. On both occasions, she was admitted to the hospital, diagnosed with Guillain-Barré syndrome (GBS) and treated with intravenous immunoglobulin, followed by partial improvement of the symptoms. Electroneuromyography revealed chronic motor axonal polyradiculoneuropathy. Magnetic resonance imaging of the brain and spine were normal. At 2 years and 10 months, the patient was referred to a pediatric neurology center, with suspicion of recurrent Guillain-Barré syndrome. Genetic testing was requested, and exome study revealed a new mutation in the CD59 gene, in homozygosity. This mutation was initially considered a variant of uncertain significance (VUS),but was later reclassified as pathogenic after immunophenotyping test revealed total CD59 deficiency. The patient was treated with Eculizumab (30 doses) and followed by a multidisciplinary team for over one year. She has not presented any new episodes of weakness and exhibited significant improvement of motor function since the beginning of the treatment. Discussion: CD59 deficiency is a rare disease characterized by the presence of chronic hemolysis and, less frequently, recurrent demyelination of the peripheral nervous system, resembling GBS. The case above presented clinical phenotype, laboratory and genotype consistent with CD59 congenital deficiency, confirmed by immunophenotyping test. Previous studies in medical literature are scarce, but have demonstrated benefit in the use of Eculizumab for the prevention of new episodes of demyelination and, in some cases, improvement of the motor deficit, which is consistent with what was observed in our patient. Final Comments: The present report demonstrated that recurrent episodes of peripheral demyelination may be associated to genetic conditions such as congenital deficiency of CD59. The genetic diagnosis allowed appropriate treatment with excellent clinical response. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: matheus_bh09@hotmail.com. Abstract Case Presentation: A previously healthy 6-year-old child presented with fever, somnolence and gait impairment. Parents sought medical attention and, due to the symptoms suggestive of infection of the central nervous system (CNS), antibiotic and antiviral therapy was performed. Within a few hours, the patient developed flaccid tetraparesis, dysphagia and motor aphasia. There was no initial improvement with antibiotics, so an immunoglobulin cycle was prescribed, with a slight improvement of symptoms. After three months, the child developed dystonic movements, especially in the face, neck and upper limbs, and chorea. She was then referred to our clinic. Infectious screening was negative, electroneuromyography and electroencephalogram were normal. Movement disorders multigenic panel showed a heterozygous variant in the ATP1A3 gene - chr19:41,970,540 G >A, compatible with rapid-onset dystonia-parkinsonism (RPD). She also developed depressive symptoms, dysarthria and learning disabilities. Currently in outpatient follow-up, using levodopa, showing a partial favorable clinical response, with progressive motor improvement, becoming more independent in daily tasks. Discussion: ATP1A3-related disorders are rare and have a broad phenotype. One of the classical presentations is RDP. It is an autosomal dominant disorder, with variable penetrance. De novo variants account for 50% of the cases. Its onset is usually in the first two decades of life and preceded by a trigger that can be infectious, psychological, head trauma, exercise, among others. Symptoms start abruptly, with bulbar symptoms, such as dysphagia and dysarthria, cranio-cervical dystonia, mild limb dystonia and bradikinesia. Cognitive impairment, executive function decline and psychiatric symptoms are also part of the disorder. Generally, this condition is not responsive to levodopa. However, our patient showed a partial favorable response, helping her regain motor abilities and walking independently again. Clinical presentation can differ in patients with the same pathogenic variants, even if they are related. Final Comments: ATP1A3-related disorders have phenotypic heterogeneity, with a broad spectrum of clinical manifestations. Clinicians should be alert to this feature in order to identify patients with a suspicious phenotype to make the diagnosis, provide genetic counseling and proper clinical management. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: amanda.mendes@discente.ufcat.edu.br. Abstract Background: Hansen's disease or leprosy is an infection caused by the Mycobacterium leprae that can affect peripheral nerves, cause severe neural damage and lead to permanent grade-2 disability. Children are particularly vulnerable not only due to their immature immune systems, but also due to the possible psychological and emotional damage as a result of the stigma associated with this disease. Objective: To describe the profile of the pediatric population with leprosy in the state of Goiás in Brazil. Methods: A retrospective descriptive epidemiological study was carried out on the notified cases of leprosy in Goiás, between 2010 and 2022. The data was collected from the Brazilian Unified Health System (SUS) databases. The age group analyzed was from 0 to 14 years. The variables evaluated were: age, sex, skin color, pregnancy, operational class and number of multidrug therapy (MDT) doses. Results: Between 2010 and 2022, 970 cases were notified in the 0-14 age group. In 2015, there were 108 cases and in 2016, 64. In 2019, the number of cases was 53. In 2020, there was a significant drop to 34 cases. This data kept decreasing to 27 cases in 2021 and 15 in 2022. Regarding the age groups, in this period, 37 cases were reported in children aged 0-4, 289 in children aged 5-9 and 644 in people aged 10-14 years. More boys (496) were affected than girls (474). The majority of the individuals had brown skin color (62,16%). In addition, there were 72 pregnancies with Hansen's disease (17 with unknown gestational age, 17 in the first, 22 in the second and 16 in the third trimester). About the operational class, 569 individuals were diagnosed with multibacillary (MB) and 395 with paucibacillary (PB) leprosy. Of the filled data with number of MDT doses, 9,6% of PB and 23,4% of MB patients didn’t complete the recommended treatment. Conclusion: This study found that the number of notified cases has been decreasing since 2015, with an accentuated drop since the pandemic started in 2020. It’s not possible to determine if this tendency is due to the reduction of the infection itself or if there has been an underreporting of new cases. However, the majority of cases are notified when the disease is already in an advanced stage, which is concerning. In addition, there is a noteworthy percentage of uncompleted treatment. Hence, prevention, early detection and treatment adherence are urgent to control this disease, especially considering Primary Care and the Family Health Strategy as public policy. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: lukasfreire15@gmail.com. Abstract Background: Spina Bifida (SB) is a congenital malformation characterized by a defect in the neural tube’s closure. Thus, as a chronic condition, its clinical complications, whether neuromotor, orthopedic or renal disorders, have an impact on morbidity rates, reflecting the need for hospitalizations. Objective: To identify the profile of hospitalized patients for SB in the Southeast region between 2017 and 2022. Methods: This is a quantitative descriptive ecological study based on data available by the Hospital Morbidity System (SIH/SUS) on DATASUS, concerning hospitalizations for SB in the Southeast region, between 2017 and 2022, using the variables: year of processing, federative unit, sex, age group 1 and ethnicity. Microsoft Excel version 2010 was used for data analysis. Results: Between January 2017 and December 2022, 2,097 hospitalizations for SB were registered in the Southeast region, with 62.42% in São Paulo (SP). There was a slight predominance of females (51.02%), maintaining the expected ratio of 1:1 between the genders. As for age group, children under 1 year of age (1,679) stand out, with 86.4% of Espírito Santo’s (ES) cases at this age. Such age hegemony ratifies the first days of a child's life as the ideal period for treatment, thus demanding hospitalization. Regarding ethnicity, there was a prevalence of White people (46.49%), especially in SP (63.33% of this state’s hospitalizations, representing 85.02% of all White patients), while Brown people prevailed in the other states. However, in Rio de Janeiro (RJ), 43.12% of the patients did not identify with any ethnicity. Finally, one can notice the lack of significant impact of the pandemic period on hospitalizations for SB in the Southeast region. Conclusion: The analyzed data reveal that most hospitalizations for SB in the Southeast region occurred in SP, with a majority of White children under 1 year of age, with a predominance of this age group in ES. Gender and the COVID-19 pandemic had negligible influence on the profile. Further studies may clarify the possible relationship of age and ethnicity with hospitalizations for SB in children. In addition, the present study analyzed only one Brazilian region, which limits the inference of similar findings in different regions, therefore requiring national studies or studies in other regions regarding the epidemiological profile of hospitalizations for SB. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: andreasayurimurata@gmail.com. Abstract Case Presentation: E.F.C.S., 2 years old, male, first child of the couple, sought our service when was 1 year and 5 months old due to regression of motor milestones from 1 year of age, which until then were age-appropriate. They denied consanguinity or similar family history. On examination, the patient presented global hypotonia, hyporeflexia, little voluntary movement, and no other alterations. Molecular research was done, positive for mitochondrial DNA depletion syndrome 2. Currently the patient is under gastrostomy, tachyostomy and multidisciplinary supervision. Discussion: Mitochondrial DNA depletion syndrome 2 or mitochondrial DNA depletion myopathy related to mitochondrial thymidine kinase (TK2) is a compound homozygous or heterozygous mutation in the TK2 gene on chromosome 16q21, has autosomal recessive inheritance, and may present with great clinical variability, from childhood onset with a rapidly progressive course with early death due to respiratory failure or late onset with slowly progressive myopathy. It mainly involves the genes H90N, I181N, H163N, I254N. The onset is usually near the age of 2 years. Among the clinical characteristics found, we have facial diplegia, hypotony, external ophthalmoplegia, myopathic stand up, diffuse muscular atrophy, delay or regression in the acquisition of motor skills, generally evolving to respiratory failure due to muscular weakness. Among the complementary exams we can observe lactic acidosis, aminoaciduria, increase of creatine kinase, electroneuromyography with myopathic alterations and muscle biopsy with torn red fibers. The diagnosis is made through molecular research. Final Comments: This case emphasizes the importance of diagnostic suspicion for better follow-up and early referral to a geneticist for genetic counseling. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

*Correspondence: alcantaraisadorac@gmail.com. Abstract Case Presentation: Female patient, one year and six months old, with a history of hospitalizations by recurrent febrile conditions, admitted due to pancytopenia, fever, jaundice, hepatosplenomegaly for 8 months. Family history that sister died with a similar condition at 4 months of life. During the hospitalization, the patient presented regression of neuropsychomotor development and ataxy, drowsiness, focal seizures. In two weeks got worse of her neurological condition and the onset of refractory seizures. The patient received therapy with metilprednisolona 30mg/kg/day however, she evolved with hemodynamic, renal, hepatic, hematological and respiratory dysfunction. It progressed to cardiorespiratory arrest and death. Laboratory tests showed: pancytopenia; hyperferritinemia 3000 mcg/L; triglyceride 333 mg/dL, fibrinogen 1,0 g/L. Myelogram showed hemophagocytic. Brain MRI showed multiple areas of signal alteration, areas of cortical rupture, foci of laminar cortical necrosis, and areas of blood-brain barrier breakdown. After all a genetic panel confirmed Familial Hemophagocytic Lymphohistiocytosis type 3 by revealing a mutation in the UNC13D gene: homozygous, variant c.3053C>A (p.Ala1018Asp). Discussion: fHLH is a rare hyperinflammatory syndrome estimated to affect approximately 1/300,000 newborns in North America. Its primary form is mostly of familial origin, associated with mutations in the PRF1, UNC13D, STX11, and STXBP2 genes, related to lymphocyte cytotoxicity. The diagnosis is based on clinical and laboratory criteria, including persistent fever, splenomegaly, cytopenia, hypertriglyceridemia, and hyperferritinemia. The treatment includes chemotherapy, immunosuppression, and hematopoietic stem cell transplant. Final Comments: fHLH is a rare and difficult to manage disease that can present similarly to common autoimmune diseases and infections. Despite having diagnostic criteria, genetic panels are of great value in the primary forms of the disease. Article published online: 12 May 2025 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil