Neuronal ceroid lipofuscinosis 11 (CLN11) presenting with early-onset cone-rod dystrophy and learning difficulties.

Neuronal Ceroid Lipofuscinosis 11 (CLN11) is an ultra-rare subtype of adult-onset Neuronal Ceroid Lipofuscinosis. Its phenotype is variable and not fully known. A 21-year-old man was evaluated in our neurogenetic outpatient clinic for early onset complex phenotype, including learning difficulties, cerebellar ataxia, cone-rod dystrophy, epilepsy, and dystonia.

Overcoming genetic neuromuscular diagnostic pitfalls in a middle-income country.

Neuromuscular disorders affect almost 20 million people worldwide. Advances in molecular diagnosis have provided valuable insights into neuromuscular disorders, allowing for improved standards of care and targeted therapeutic approaches. Despite this progress, access to genomic diagnosis remains scarce and inconsistent in middle-income countries such as Brazil.

Exploring cognitive functions and brain structure in Hereditary Transthyretin amyloidosis using brain MRI and neuropsychological assessment.

Background: Central nervous system symptoms, such as cognitive dysfunction, have been reported in Hereditary Transthyretin Amyloidosis (ATTRv). However, there is a lack of neuroimaging studies investigating structural alterations in the brain related to cognition in ATTRv amyloidosis. This study aimed to investigate cognition and cortical morphology in a cohort of ATTRv patients.

Integrated Approaches and Practical Recommendations in Patient Care Identified with 5q Spinal Muscular Atrophy through Newborn Screening.

In recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and skeletal deformities. Recognizing the pre-symptomatic phases supported by screening and confirmatory genetic tests is crucial for early diagnosis.

Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil (REACT-SP).

Background: Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetic profile of patients enrolled in the Transthyretin Cardiac Amyloidosis Registry of the State of São Paulo, Brazil.

Prevalence and Diagnostic Journey of Friedreich's Ataxia in the State of São Paulo, Brazil.

Friedreich's Ataxia (FRDA) is the leading cause of ataxia worldwide, but data on epidemiology and diagnostic journey are scarce, particularly in Latin America. Herein we estimated the prevalence of FRDA in the most populous Brazilian state and characterized the diagnostic odyssey of the disease. We received anonymized data of patients with FRDA from advocacy groups and physicians.

Dominant mutations causing axonal Charcot-Marie-Tooth disease expand -associated diseases.

Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited peripheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl-tRNA synthetase () cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy.

Gene-based therapies for neuromuscular disorders.

Neuromuscular diseases (NMD) include a broad group of medical conditions with both acquired and genetic causes. In recent years, important advances have been made in the treatment of genetically caused NMD, and most of these advances are due to the implementation of therapies aimed at gene regulation. Among these therapies, gene replacement, small interfering RNA (siRNA), and antisense antinucleotides are the most promising approaches.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy.

Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the . SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the gene or adding a copy of the gene through gene therapy, providing a drastic change in the natural history of the disease.

Cranial Nerve Thinning Distinguishes RFC1-Related Disorder from Other Late-Onset Ataxias.

Background: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear.

Objectives: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C.

Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease.

RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat.

Nigrostriatal dysfunction in RFC1-related disorder/CANVAS.

Introduction: Parkinsonism is now recognized as an additional feature in RFC1/CANVAS syndrome; however, no systematic evaluation of nigrostriatal dopaminergic function has been published so far.

Methods: This is an observational, single-center study, which analyzed 13 patients with molecular confirmation of RFC1/CANVAS. Disease severity was assessed with the SARA scale.

Frequency of GAA- Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia.

Objectives: Intronic GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA- ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA- ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis.

Morphological and morphometric study of the superior vestibular nerve trunk in guinea pigs.

The guinea pig has been chosen as a research model for otologic or neuropathic studies due to the relative ease of the cochlea, cochlear nerve, and vestibular nerve dissection. Little data have been reported on the normality of these nerves. The vestibular nerve is composed of the superior vestibular, inferior vestibular, and branch nerves.

Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings.

Spinocerebellar ataxias (SCAs) have a worldwide average prevalence of 2.7 cases per 100,000 individuals, with significant geographic variability. This study aimed to develop resource-limited strategies to detect and characterize the frequency and genetic-clinical profile of SCAs in an unexplored population from Alagoas State, a low Human Development Index state in northeastern Brazil.

Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs.

COQ7 encodes a hydroxylase responsible for the penultimate step of coenzyme Q10 (CoQ10) biosynthesis in mitochondria. CoQ10 is essential for multiple cellular functions, including mitochondrial oxidative phosphorylation, lipid metabolism, and reactive oxygen species homeostasis. Mutations in COQ7 have been previously associated with primary CoQ10 deficiency, a clinically heterogeneous multisystemic mitochondrial disorder.