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.

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.

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 experts' consensus on the treatment of infantile epileptic spasm syndrome in infants.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. OBJECTIVE: To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. METHODS: An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. RESULTS: Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. CONCLUSION: Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

ANTECEDENTES: A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. OBJETIVO: Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. MéTODOS: Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. RESULTADOS: Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. CONCLUSãO: O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants / Consenso de especialistas brasileiros sobre o tratamento da síndrome dos espasmos infantis em lactentes

Abstract Background Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. Objective To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. Methods An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. Results Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. Conclusion Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

Resumo Antecedentes A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. Objetivo Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. Métodos Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. Resultados Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. Conclusão O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

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.

Functional results after carpal tunnel release in mucopolysaccharidosis.

BACKGROUND: Mucopolysaccharidosis consists of a group of diseases caused by the deficiency of lysosomal enzymes, which may lead to the compression of the median nerve in the carpal tunnel due to the accumulation of glycosaminoglycan, resulting in the hand disability. The study purpose is to present functional results of carpal tunnel release in mucopolysaccharidosis patients. Patients were selected from an enzyme replacement group in the Department of Pediatric Neurology. The legal guardians of the patients were informed about the likely functional change of the hands induced by compression of the median nerve. Clinical evaluation was performed in those patients who received their legal guardians' consent to participate and was included inspection, assessment of functional level, wrinkle test and the digital pinch function to manipulate small and large objects. Ultrasound and electromyography were performed to confirm the clinical median nerve compression. Bilateral extended opening technique was performed to access the carpal tunnel and analyze the anatomic findings of the median nerve and the flexed tendons of the fingers. After the surgical release of the carpal tunnel, the clinical evaluation was repeated. Subjective observations of the legal guardians were also considered. RESULTS: Seven patients underwent bilateral surgical opening of the carpal tunnel; six boys, mean age of 9.5 (5 to 13), five of them presenting Type II mucopolysaccharidosis, 1 Type I and 1 Type VI. The average follow-up was 12 months (10-13 months). The functional results observed included the improvement in the handling of small and large objects in all children who underwent decompression of the median nerve. The comparison between the pre-operative and post-operative functional levels revealed that 2 patients evolved from Level II to IV, 3 from Level III to IV, 1 from Level IV to V and 1 patient remained in Level III. Tenosynovitis around the flexor tendons and severe compression of the median nerve in the fourteen carpal tunnels were observed during the surgical procedure. In 6 wrists, partial tenosynovitis was performed. CONCLUSIONS: Despite the improvement in the overall function of the children' hands, we cannot conclude that only surgery was responsible for the benefit. Better designed studies are required.

Mucopolysacaridosis type iiib misdiagnosed as an autistic spectrum disorder: a case report and literature review / Mucopolissacaridose tipo iii b mal diagnosticada como transtorno de espectro autista: relato de caso e revisão de literatura

ABSTRACT Objective: To report a rare case of mucopolysaccharidosis IIIB in a pediatric patient, with emphasis on the description of the clinical manifestations and the early diagnosis. Case description: A 14-year-old male patient, who presented regression of neuropsychomotor development since his three years and six months old, with speech loss and frequent falls, evolving with behavioral changes, with agitation and aggressiveness. Although being diagnosed with autism, there was no response to the established treatment; he was subsequently submitted to metabolic investigation, which lead to the diagnosis of Mucopolysaccharidosis IIIB. Comments: Identifying a metabolic disorder requires connecting multiple signs and symptoms, as well as eliminating other apparent causes. MPS IIIB is a diagnostic challenge, particularly in the early stages and in the absence of a family history of the disease.

RESUMO Objetivo: Relatar o caso raro de um paciente pediátrico com mucopolissacaridose III B, com ênfase na descrição de manifestações clínicas. Descrição do caso: Paciente masculino de 14 anos que, a partir dos 3 anos e 6 meses de idade, apresentou regressão do desenvolvimento neuropsicomotor, com perda da fala e quedas frequentes, evoluindo com alterações comportamentais, agitação e agressividade. Diagnosticado como autista, não obteve resposta ao tratamento estabelecido, sendo posteriormente submetido à investigação metabólica, que evidenciou o diagnóstico de mucopolissacaridose III B. Comentários: A identificação de um distúrbio metabólico exige conectar vários sinais e sintomas, além de eliminar outras causas aparentes. A mucopolissacaridose III B é um desafio diagnóstico, particularmente nos estágios iniciais e na ausência de história familiar da doença.

Pediatric Anti-N-methyl-D-aspartate Receptor Encephalitis Mimicking Glutaric Aciduria Type 1: A Case Report.

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.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1ß, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. RESULTS: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. CONCLUSION: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

MUCOPOLYSACARIDOSIS TYPE IIIB MISDIAGNOSED AS AN AUTISTIC SPECTRUM DISORDER: A CASE REPORT AND LITERATURE REVIEW.

OBJECTIVE: To report a rare case of mucopolysaccharidosis IIIB in a pediatric patient, with emphasis on the description of the clinical manifestations and the early diagnosis. CASE DESCRIPTION: A 14-year-old male patient, who presented regression of neuropsychomotor development since his three years and six months old, with speech loss and frequent falls, evolving with behavioral changes, with agitation and aggressiveness. Although being diagnosed with autism, there was no response to the established treatment; he was subsequently submitted to metabolic investigation, which lead to the diagnosis of Mucopolysaccharidosis IIIB. COMMENTS: Identifying a metabolic disorder requires connecting multiple signs and symptoms, as well as eliminating other apparent causes. MPS IIIB is a diagnostic challenge, particularly in the early stages and in the absence of a family history of the disease.

Acute Childhood Viral Encephalitis in Southern Brazil.

BACKGROUND: Viral meningoencephalitis is highly heterogeneous, varying by geographic location. The aim of this study was to characterize the etiology and reporting the clinical findings and outcome of viral encephalitis in children in southern Brazil. METHODS: A cross-Sectional study was conducted at Hospital Pequeno Príncipe, Curitiba, Brazil, between January 2013 and December 2017. It included patients younger than 18 years, who fulfilled the criteria: altered mental status as a major criteria and 2 or more minor criteria (1) fever, (2) seizures, (3) focal neurologic findings, (4) central system fluid white cell count of ≥5 cells/mm, (5) abnormal brain imaging, and/or (6) electroencephalogram abnormalities. RESULTS: Viral meningoencephalitis was diagnosed in 270 children, with median age of 2 years (interquartile range: 0-4), The etiology of viral meningoencephalitis was confirmed in 47% of patients. Enterovirus (18%) was the major cause of encephalitis in Southern Brazilian children, and a high prevalence of Epstein-Barr virus (6%) was demonstrated. Most patients presented with fever (81%), followed by vomiting (50%), focal neurologic findings (46%), seizures (31%) and headache (30%). Few abnormalities were detected on electroencephalograms and brain magnetic resonance images. On discharge from hospital, symptoms resolved completely in 87% of children. Sequelae were mainly observed in patients with focal neurologic symptoms (P<0.001), presence of seizures (P<0.001) and electroencephalogram abnormalities (P=0.024). CONCLUSIONS: Enterovirus was the major cause of encephalitis. Etiologic agent of encephalitis seems to be influenced by the local virologic pattern. A poor outcome was identified in patients with seizures, focal neurologic findings and electroencephalogram abnormalities.

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.

X-linked adrenoleukodystrophy in brazil: a case series / Adrenoleucodistrofia ligada ao x no brasil: uma série de casos

ABSTRACT Objective: To describe patients with different phenotypes of X-linked adrenoleukodystrophy: pre-symptomatic, cerebral demyelinating inflammatory adrenoleukodystrophy, adrenomyeloneuropathy and adrenal insufficiency only. Methods: Specific data related to epidemiology, phenotype, diagnosis and treatment of 24 patients with X-linked adrenoleukodystrophy were collected. A qualitative cross-sectional and descriptive-exploratory analysis was performed using medical records from a reference center in Neuropediatrics in Curitiba, Brazil, as well as an electronic questionnaire. Results: The majority (79%) of patients had cerebral demyelinating inflammatory adrenoleukodystrophy, presenting aphasia, hyperactivity and vision disorders as the main initial symptoms. These symptoms appeared, on average, between six and seven years of age. There was a mean delay of 11 months between the onset of symptoms/signs and the diagnosis. Patients sought diagnosis mainly with neuropediatricians, and the main requested tests were dosage of very long chain fatty acids and brain magnetic resonance. Conclusions: All phenotypes of X-linked adrenoleukodystrophy, except for myelopathy in women, were presented in the studied population, which mainly consisted of children and adolescents. Prevalent signs and symptoms registered in the literature were observed. Most of the patients with cerebral demyelinating inflammatory adrenoleukodystrophy were not diagnosed in time for hematopoietic stem cell transplantation.

RESUMO Objetivo: Descrever pacientes com diferentes formas de adrenoleucodistrofia ligada ao X: pré-sintomática, adrenoleucodistrofia inflamatória desmielinizante cerebral, adrenomieloneuropatia e insuficiência adrenal primária. Métodos: Dados específicos relacionados a epidemiologia, fenótipo, diagnóstico e tratamento de 24 pacientes com adrenoleucodistrofia ligada ao X foram coletados. Realizou-se análise qualitativa, transversal e descritivo-exploratória, utilizando prontuários de um centro de referência em neuropediatria de Curitiba, Brasil, além de um questionário eletrônico. Resultados: A maioria (79%) dos pacientes manifestou adrenoleucodistrofia inflamatória desmielinizante cerebral, apresentando afasia, hiperatividade e distúrbios da visão como principais sintomas iniciais, que apareceram, em média, entre seis e sete anos de idade. Houve um atraso médio de 11 meses entre o início das manifestações e o diagnóstico. Os pacientes procuraram diagnóstico principalmente com neuropediatras, e os principais exames solicitados foram dosagem de ácidos graxos de cadeia muito longa e a ressonância magnética de crânio. Conclusões: Todos os fenótipos da adrenoleucodistrofia ligada ao X, exceto mielopatia em mulheres, foram apresentados na amostra estudada, composta principalmente de crianças e adolescentes. Foram observados sinais e sintomas prevalentes na literatura. A maioria dos pacientes com adrenoleucodistrofia inflamatória desmielinizante cerebral não recebeu diagnóstico em tempo hábil para a realização de transplante de medula óssea.

Clinical findings in Brazilian patients with adult GM1 gangliosidosis.

GM1 gangliosidosis is a lysosomal storage disorder caused by ß-galactosidase deficiency. To date, prospective studies for GM1 gangliosidosis are not available, and only a few have focused on the adult form. This retrospective cross-sectional study focused on clinical findings in Brazilian patients with the adult form of GM1 gangliosidosis collected over 2 years. Ten subjects were included in the study. Eight were males and two females, with median age at diagnosis of 11.5 years (IQR, 4-34 years). Short stature and weight below normal were seen in five out of the six patients with data available. Radiological findings revealed that the most frequent skeletal abnormalities were beaked vertebrae, followed by hip dysplasia, and platyspondyly. Neurological examination revealed that dystonia and swallowing problems were the most frequently reported. None of the patients presented hyperkinesia, truncal hypertonia, Parkinsonism, or spinal cord compression. Clinical evaluation revealed impairment in activities of cognitive/intellectual development and behavioral/psychiatric disorders in all nine subjects with data available. Language/speech impairment (dysarthria) was found in 8/9 patients, fine motor and gross motor impairments were reported in 7/9 and 5/9 patients, respectively. Impairment of cognition and daily life activities were seen in 7/9 individuals. Our findings failed to clearly identify typical early or late alterations presented in GM1 gangliosidosis patients, which confirms that it is a very heterogeneous condition with wide phenotypic variability. This should be taken into account in the evaluation of future therapies for this challenging condition.

X-LINKED ADRENOLEUKODYSTROPHY IN BRAZIL: A CASE SERIES.

OBJECTIVE: To describe patients with different phenotypes of X-linked adrenoleukodystrophy: pre-symptomatic, cerebral demyelinating inflammatory adrenoleukodystrophy, adrenomyeloneuropathy and adrenal insufficiency only. METHODS: Specific data related to epidemiology, phenotype, diagnosis and treatment of 24 patients with X-linked adrenoleukodystrophy were collected. A qualitative cross-sectional and descriptive-exploratory analysis was performed using medical records from a reference center in Neuropediatrics in Curitiba, Brazil, as well as an electronic questionnaire. RESULTS: The majority (79%) of patients had cerebral demyelinating inflammatory adrenoleukodystrophy, presenting aphasia, hyperactivity and vision disorders as the main initial symptoms. These symptoms appeared, on average, between six and seven years of age. There was a mean delay of 11 months between the onset of symptoms/signs and the diagnosis. Patients sought diagnosis mainly with neuropediatricians, and the main requested tests were dosage of very long chain fatty acids and brain magnetic resonance. CONCLUSIONS: All phenotypes of X-linked adrenoleukodystrophy, except for myelopathy in women, were presented in the studied population, which mainly consisted of children and adolescents. Prevalent signs and symptoms registered in the literature were observed. Most of the patients with cerebral demyelinating inflammatory adrenoleukodystrophy were not diagnosed in time for hematopoietic stem cell transplantation.

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.

Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America.

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase(®), Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.

Avaliação audiológica de pacientes com mucopolissacaridose em um hospital pediátrico / Audiologic evaluation of patients with mucopolysaccharidosis at a pediatric hospital

Introdução: Mucopolissacaridoses são caracterizadas pela deficiência de enzimas lisossomais que degradam glicosaminoglicanos. O acúmulo destes metabólitos causa alterações variadas, entre elas, alterações otológicas. Objetivo: Avaliar uma série de pacientes com mucopolissacaridose no Hospital Pequeno Príncipe, enfatizando suas alterações audiológicas e estabelecer um protocolo permanente de avaliação desses pacientes. Método: Estudo retrospectivo da avaliação audiológica através de 18 prontuários de pacientes com diagnóstico de mucopolissacaridose atendidos no Hospital Pequeno Príncipe entre janeiro de 2005 e novembro de 2010. Resultados: Foram selecionados sete prontuários, destes, apenas um não apresentava perda auditiva, sendo que a maioria apresentava perda do tipo condutiva ou mista e apenas um perda exclusivamente neurossensorial. Seis destes pacientes também haviam sido submetidos a pelo menos um procedimento otorrinolaringológico. Conclusão: Os pacientes com mucopolissacaridose requerem cuidados permanentes e acompanhamento multidisciplinar. O otorrinolaringologista pediátrico ocupa importante papel tanto na avaliação otológica e audiológica quanto no manejo das vias aéreas, já que quase a totalidade dos pacientes avaliados apresentavam algum tipo de perda auditiva e indicação de procedimentos otorrinolaringológicos. O padrão definido em nosso serviço foi de ao menos uma consulta inicial quando houver suspeita e/ou diagnóstico da MPS e consultas sequenciais, no mínimo semestrais, ou mais frequentes conforme necessidade.

Introduction: Mucopolysaccharidosis are characterized by the deficit of lysosomal enzymes corrupting the glycosaminoglycans. Accumulating these metabolites causes several alterations, such as otologic alterations. Objective: To evaluate a number of patients with mucopolysaccharidosis at Pequeno Principe Hospital, emphasizing their audiologic alterations and establish a permanent evaluation protocol for these patients. Method: A backward-looking study of audiologic evaluation by using records of 18 patients diagnosed with mucopolysaccharidosis and attended at Pequeno Principe Hospital between January 2005 and November 2010. Results: 7 records were selected, out of which only one did not have a hearing loss, and most of them presented conductive or mixed hearing loss, and only one had an exclusively sensorineural loss. Six of these patients had also been submitted to at least one otorhinolaryngological procedure. Conclusion: Mucopolysaccharidosis patients require a permanent care and a multidisciplinary follow-up. The pediatric otorhinolaryngologist plays an important role when performing the otologic and audiologic evaluation and managing the airways, since almost all the patients evaluated presented some kind of hearing loss and an indication of otorhinolaryngologic procedure. The pattern determined in our service was at least an initial consultation when there is a suspicion and/or diagnosis of MPS and sequential consultations that were at least twice a year or more frequent, if necessary.