Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA- encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we established an optimized ribosome profiling approach tailored for the unique features of the human mitoribosome. Analysis of ribosome footprints in five cell types revealed that average mitochondrial synthesis rates corresponded precisely to cytosolic rates across OXPHOS complexes. Balanced mitochondrial and cytosolic synthesis did not rely on rapid feedback between the two translation systems. Rather, LRPPRC, a gene associated with Leigh's syndrome, is required for the reciprocal translatomes and maintains cellular proteostasis. Based on our findings, we propose that human mitonuclear balance is enabled by matching OXPHOS subunit synthesis rates across cellular compartments, which may represent a vulnerability for cellular proteostasis.

Leigh Syndrome in an Adolescent Girl: A Case Report

Leigh syndrome (LS) is a disorder of infancy and rarely late childhood. It presents with regression of mental and motor skills. Here, we present LS in an adolescent girl who presented with generalized dystonia and cognitive decline. Her infective, metabolic, endocrinal and autoimmune work up was normal. The neuroimaging showed progressive symmetric involvement of basal ganglia with focal intensity over bilateral lentiform nucleus and thalamic region. The cerebrospinal fluid (CSF) lactate level was elevated. Genetic test could not be performed; however the history of neuro-regression with extrapyramidal involvement with CSF and neuroimaging finding led to the diagnosis of Leigh’s syndrome.

Pediatric physical therapy intervention in leigh’s syndrome: a clinical case report

Objetivo: o objetivo deste estudo de caso foi descrever uma intervenção fisioterapêutica em um menino de 5 anos com Síndrome de Leigh (LS). Método: o equilíbrio foi testado por meio da Escala de Equilíbrio Pediátrico (PBS) e a função nas atividades da vida diária foi medida com a avaliação Pediátrica do Inventário de Incapacidade (PEDI). Além disso, a distribuição da pressão plantar (PPD) foi medida durante uma velocidade auto selecionada, caminhando em uma plataforma de detecção capacitiva. A intervenção baseou-se no uso de cinesioterapia, recursos sensoriais e proprioceptivos, em sessões de 50 minutos, duas vezes por semana, durante 10 semanas. Resultados: O presente estudo demonstrou ganhos para a criança em relação ao equilíbrio durante a marcha. Da mesma forma, foi observada a melhora do controle postural, planejamento de tarefas e outras habilidades. Conclusão: A intervenção fisioterapêutica neste relato de caso para a Síndrome de Leigh foi eficaz e poderia servir de base para estudos futuros ou intervenção em terapia clínica que segue esse tipo de tratamento.

Biotin-Thiamine Responsive Encephalopathy: Report of an Egyptian Family with a Novel SLC19A3 Mutation and Review of the Literature

Biotin-thiamine responsive basal ganglia disease (BTRBGD) is an autosomal recessive neurometabolic disorder with poor genotype-phenotype correlation, caused by mutations in the SLC19A3 gene on chromosome 2q36.6. The disease is characterized by three stages: stage 1 is a sub-acute encephalopathy often triggered by febrile illness; stage 2 is an acute encephalopathy with seizures, loss of motor function, developmental regression, dystonia, external ophthalmoplegia, dysphagia, and dysarthria; stage 3 is represented by chronic or slowly progressive encephalopathy. Clinical and biochemical findings, as well as the magnetic resonance imaging (MRI) pattern, resemble those of Leigh's syndrome, so that BTRBGD can be misdiagnosed as a mitochondrial encephalopathy.Here we report the clinical and radiological phenotypes of two siblings diagnosed with BTRBGD in which a novel SLC19A3 mutation (NM_025243.3: c.548C > T; p.Ala183Val) was found by whole exome sequencing (WES) of the family members.

Leigh Syndrome: Report of a Rare Case with Late Onset Presentation

Leigh's syndrome, or sub acute necrotizing encephalomyelopathy, is a rare inherited neurometabolic disease of infancy and early childhood with variable course and prognosis. Rarely, it occurs in juveniles and adults. The diagnosis is difficult and still remains to challenge the clinicians on the basis of history; hence the role of imaging is very essential. It is the neuroimaging, chiefly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the diagnosis. Late-onset varieties are rare and only few cases were reported all over the world. Here, I report a case of late onset (juvenile) Leigh syndrome presenting with an acute polyneuropathy. Neuroimaging confirmed it to be a case of Leigh syndrome.