Movement disorders in GLUT1 deficiency syndrome: a systematic review of the literature

Clinical and Genetic Spectrum of ATP1A3-Related Disorders

The results highlight the need for a unified diagnostic framework for ATP1A3-related disorders and demonstrate the feasibility and scientific value of coordinated rare disease research in resource-limited settings.

Glucose Transporter Deficiency Syndrome Type 1 (Glut1‐DS): New Insights From a Brazilian Cohort of Patients

ABSTRACT Glucose transporter deficiency syndrome type 1 (Glut1‐DS) is a rare neurometabolic disorder caused by pathogenic variants in SLC2A1, characterized by epilepsy, neurodevelopmental delay, movement disorders, dysarthria, intellectual disability, and postnatal microcephaly. We aimed to characterize the natural history of a Brazilian cohort of patients with Glut1‐DS. Brazilian patients of all ages were included if they presented with clinical features consistent with Glut1‐DS and carried a pathogenic or likely pathogenic SLC2A1 variant. Forty patients were included (21 males; median age 9.1 years [IQR: 6.0–12.9]; median age at diagnosis 5.0 years [IQR: 3.0–9.9]), of whom 32 had the classical phenotype. The most frequent manifestations at inclusion were seizures (37/40), speech delay (34/40), and movement disorders (29/35). Thirty‐four patients (85%) were receiving ketogenic dietary therapy (27 classical ketogenic diet and 7 modified Atkins diet). Cerebrospinal fluid analysis was performed in 10 patients (27.5%), all of whom had hypoglycorrhachia. Genetic testing identified 31 distinct SLC2A1 variants, including 15 novel variants. Intrafamilial phenotypic variability was observed in one of four families with recurrent disease, and reduced penetrance was identified in one affected parent. Missense variants were generally associated with milder phenotypes than truncating variants. These findings expand the phenotypic and genotypic spectrum of Glut1‐DS, highlight the high proportion of previously unreported SLC2A1 variants in the Brazilian population, and reinforce the importance of comprehensive genetic evaluation and counseling for affected families.

Uncovering Neuropathic Pain in CANVAS: Lessons from a Case-Based Literature Review.

INTRODUCTION Cerebellar ataxia with neuronopathy and vestibular areflexia syndrome (CANVAS) is a rare, late-onset neurodegenerative disorder caused by biallelic intronic AAGGG repeat expansions in the RFC1 gene. Its phenotype is heterogeneous, ranging from isolated sensory neuronopathy to the full clinical triad. Although neuronopathy is present in the majority-if not all-of the cases, the prevalence and clinical significance of neuropathic pain remain insufficiently characterized. METHODS We report a genetically confirmed case of CANVAS in a 58-year-old woman presenting predominantly with asymmetrical neuropathic pain. Clinical, neurophysiological, vestibular, and genetic assessments were performed, with longitudinal follow-up over 3 years. Additionally, a case-driven systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted in May 2026 in two databases (MEDLINE and Scopus) that identified cohorts of CANVAS cases with data on pain. Fourteen studies met our inclusion criteria. Pooled prevalence of neuropathic pain was calculated using a random-effects model. RESULTS The systematic review included 445 patients with CANVAS. The pooled prevalence of neuropathic pain was 43.2% (95% confidence intervals 34.0-52.9%) with moderate heterogeneity across these studies (I2 = 65%). Evidence from included studies suggests that pain may occur early and represents a significant contributor to disease burden. CONCLUSIONS Neuropathic pain is a frequent and potentially early manifestation of CANVAS, likely reflecting underlying sensory neuronopathy. CANVAS should be considered in patients with idiopathic sensory neuronopathy, even when pain is present. Early recognition and targeted genetic testing are essential to improve diagnosis and optimize patient management in this underdiagnosed condition.

Neurological, Neurodevelopmental and Treatment Outcomes in Patients With Pyruvate Dehydrogenase Complex Deficiency

ABSTRACT Objective The aim of this study was to characterize intellectual and motor function, neurological features including epilepsy, treatment response, and adaptive behavior in patients with pyruvate dehydrogenase complex deficiency (PDCD) in Sweden. Methods Forty‐two individuals with genetically confirmed PDCD (86% PDHA1‐related disease) were identified from a nationwide epidemiological study and were included in this cross‐sectional study comprising systematic neurological evaluations (n = 41) and caregiver interviews assessing adaptive behavior (n = 35). Results Intellectual disability was detected in 33/42 (79%) individuals, while 31/35 (89%) demonstrated significant impairments in adaptive functioning. Although 27/39 (69%) were ambulatory, only 8/39 (21%) demonstrated age‐appropriate walking ability. Clinical signs of polyneuropathy were observed in 24/41 (59%), bulbar symptoms in 22/41 (54%), spasticity in 19/41 (46%), ataxia in 13/41 (32%), and dystonia in 9/41 (22%). Lifetime epilepsy was present in 16/41 (39%) of individuals. Ketogenic diet treatment, administered to 30 individuals, was effective in both prenatal‐ and postnatal‐onset disease. Seizure frequency decreased in individuals with epilepsy (8/9; 89%) and relapses of dystonia, ataxia, exercise intolerance, and lactic acidosis were prevented in all affected individuals (15/15). Improvements in communication and motor function were also noted. Discussion Intellectual disability and deficits in adaptive behavior are frequent in PDCD, although cognitive outcomes are more heterogeneous among individuals with postnatal onset. Prenatal onset and epilepsy are associated with severe‐profound intellectual disability. Although most are ambulatory, motor deficits are frequent. A ketogenic diet treatment is a safe and effective therapeutic option, contributing to both seizure control and remission of neurological deterioration relapses.

KBG syndrome: A scoping review of electroclinical features of patients with epilepsy.

Epileptic seizures in patients with KBG syndrome are usually generalized and have an onset between infancy and mid-teens, and common epileptological features in KBG syndrome comprise the good response to antiseizure medication and, in most cases, the remitting nature of epilepsy.

Clinical and genetic findings in Parkinson’s disease in a Turkish cohort: a retrospective exome sequencing study