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.

Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p<0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p=0.598) and the total of negative samples for the remaining viruses tested (p=0.614). There was a significant association in the occurrence of infection in children aged 0-12 months for the condition 1 (p=0.030) as well as condition 2 (p=0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal distribution. These data indicate the significant involvement of HAdV-F type 41 in the etiology of ADD in Minas Gerais, which demonstrates the importance of other viral agents in the development of the disease after the introduction of rotavirus vaccine immunization.

To evaluate the prevalence and circulation of rotavirus genotypes before and after the introduction of oral vaccine against human rotavirus, and to check for a possible change in the age of occurence of the infection by RV-A. This was a cross-sectional study conducted between 2002-2011, in the city of Juiz de Fora, state of Minas Gerais, Brazil. A total of 1,144 diarrheal stool specimens were obtained from nonhospitalized children aged between 0 and 5 years, and analyzed by polyacrylamide gel electrophoresis and reverse-transcription polymerase chain reaction for genotype characterization. Data on prevalence and age distribution of rotavirus cases were analyzed through the chi-squared test (p < 0.05), using SPSS, release 13.0. Rotavirus infection was detected in 9.35% (107/1,144) samples, with prevalence rates ranging from 11.12% (90/809) in the pre-vaccine to 5.07% (17/335) in the post-vaccine period (p = 0.001). Among the samples tested, the most frequently detected genotypes were G1P[6] (6/33 = 18.2%) in the period between 2002 and 2005 and G2P[4] in 2006 (11/33 = 33.3%) and in the period between 2007 and 2011 (5/33 = 15.2%). There was also a significant reduction in the number of cases of rotavirus disease in children aged between 0 and 36 months after the vaccine introduction. The study evidenced a significant decrease in the prevalence of rotavirus, mainly in children aged between 0 and 36 months in the 2007-2011 period, as well as a reduction in G1 genotype circulation.

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.

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.