Rare Research Report

New research from the Brain Vascular Malformation Consortium (BVMC). This summary is based on a paper published in the Orphanet Journal of Rare Diseases on August 28, 2025, titled "Assessing racial differences in North American hereditary hemorrhagic telangiectasia study recruitment and care." Read the paper here. Learn more about BVMC. Transcript: New research from the Brain Vascular Malformation Consortium (BVMC), a research group of the Rare Diseases Clinical Research Network.Assessing Disparities in Access to Clinical Care and Research for Patients with Hereditary Hemorrhagic Telangiectasia.This summary is based on a paper published in the Orphanet Journal of Rare Diseases on August 28, 2025.Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of the blood vessels that can cause excessive bleeding. Patients with rare diseases like HHT are more likely to experience increased health outcome disparities due to inequitable healthcare.In this study, researchers assessed disparities in access to clinical care and research for patients with HHT. First, the team collected race data from BVMC study recruits at HHT clinics in Toronto and San Francisco. Next, they compared the racial differences between HHT patients recruited for research and HHT patients in the general population.Results reveal preliminary evidence of racial differences between HHT center clinic patients and surrounding populations. Findings also show an association between race and enrollment to HHT research studies. Authors note that this study lays the foundation for beginning to address disparities in HHT care and research.

New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the Journal of Child Neurology in November 2025 titled "Exploration Into Lived Experiences of Multiple Sulfatase Deficiency–Affected Individuals and Their Families." Read the paper here. Learn more about GLIA-CTN. Transcript: New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN), a research group of the Rare Diseases Clinical Research Network.Working with Caregivers to Capture Lived Experiences of Children with Multiple Sulfatase Deficiency.This summary is based on a paper published in the Journal of Child Neurology in November 2025.Rare diseases deeply affect children and families, but their experiences are only incompletely understood—especially for extremely rare conditions like multiple sulfatase deficiency (MSD), a leukodystrophy.In this study, researchers worked directly with caregivers to capture lived experiences of children with MSD. Nineteen caregivers shared information about their child’s daily skills, emotional health, and overall quality of life, as well as their own well-being. The team used several established questionnaires to measure these areas and compared the results to data from metachromatic leukodystrophy (MLD), a related rare disorder.Results showed that although children with MSD face significant challenges with daily activities, caregivers reported that emotional well-being was a strength, underscoring the incredible resiliency of the rare disease community. When the team used caregiver-centered tools, they captured a richer picture of what matters most to families, such as coordination of care and emotional support. Caregivers themselves experienced major emotional and practical strain, often feeling grief and isolation, similar to those caring for children with MLD.Authors note that these insights show why including patient and caregiver perspectives in research is critical. Their input helps identify meaningful outcomes, improves the design of clinical trials, and ensures that future treatments focus on what truly matters to families.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America on October 21, 2025, titled "Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology." Read the paper here. Learn more about MGNet. Transcript: New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.Evaluating the Therapeutic Potential of Immunoglobin G- and Immunoglobin M-Specific Proteases in Acetylcholine Receptor-Positive Myasthenia Gravis.This summary is based on a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America on October 21, 2025.Myasthenia gravis (MG) is an autoimmune neuromuscular disorder in which antibodies targeting the acetylcholine receptor (AChR) cause muscle weakness. Current therapies help many patients, but some remain refractory, underscoring the need for more personalized approaches.In this study, researchers evaluated the therapeutic potential of S-1117, a pan-IgG–specific protease engineered to selectively cleave the Fcγ region of pathogenic AChR-IgG. Using live cell-based assays with monoclonal autoantibodies and patient serum, the team showed that S-1117 effectively impaired IgG-mediated complement activation on AChR-expressing cells.Importantly, the work uncovered a previously unrecognized MG subset driven by pathogenic AChR-IgM, which either amplified IgG-mediated injury or served as the primary source of complement activation. An IgM-specific protease fully suppressed IgM-driven pathogenicity, and combining IgG- and IgM-targeted enzymes achieved broader inhibition.These findings reveal critical disease heterogeneity in MG and highlight Ig-specific proteases as a promising precision-medicine strategy to improve treatment for patients with antibody-mediated weakness.

New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the journal Human Gene Therapy on September 12, 2025, titled "Deep Intronic SVA_E Retrotransposition as a Novel Factor in Canavan Disease Pathogenesis." Read the paper here. Learn more about GLIA-CTN. Transcript: New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN), a research group of the Rare Diseases Clinical Research Network.Discovering a New Pathogenic Variant in Canavan Disease. This summary is based on a paper published in the journal Human Gene Therapy on September 12, 2025.Canavan disease is a progressive type of leukodystrophy caused by variants in the ASPA gene. In patients with Canavan disease, increased levels of N-acetylaspartic acid lead to symptoms including developmental delay, abnormal muscle tone, and macrocephaly (larger than typical head size). In order for patients to receive a complete diagnosis, all pathogenic variants in the ASPA gene must be identified.In this study, researchers discovered a new pathogenic variant in Canavan disease. First, the team identified five patients with a clinical and biochemical diagnosis of Canavan disease, but no second pathogenic variant. Next, they used the gene editing tool CRISPR-Cas9 and long-read sequencing technique to analyze the gene structure of ASPA in these patients.Results revealed a previously unidentified variant of the ASPA gene involving the insertion of an SVA_E retrotransposon into intron 4 of the ASPA gene. Authors note that these findings can improve genetic counseling for families and increase access to gene therapy trials.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Annals of Neurology on September 6, 2025, titled "A Distinct Immunological Signature in Late-Onset Myasthenia Gravis: Insights from an Exploratory Proteomics Study." Read the paper here. Learn more about MGNet. Transcript: New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.Comparing Differences in Proteins Among Patients with Early-Onset and Late-Onset Myasthenia Gravis.This summary is based on a paper published in the journal Annals of Neurology on September 6, 2025.Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Patients with early-onset MG develop symptoms before age 50, while patients with late-onset MG develop symptoms after age 50. Not much is known about how early-onset and late-onset MG affect the body differently.Utilizing sera (the liquid part of blood that remains after coagulation) from the NIH-sponsored BeatMG clinical trial and MGNet, researchers performed proteomics analysis of 768 inflammatory proteins and uncovered a distinct immunological signature that differentiates late-onset from early-onset myasthenia gravis.Pathways linked to leukocyte differentiation and myeloid cell migration were enriched in late-onset disease. Seven proteins were further replicated in the UK Biobank, and IL18R1, CXCL17, and CCL11 were validated in an independent cohort that were specific to late-onset MG. Investigators note that further studies are needed to confirm the use of these proteins as biomarkers of late-onset MG, as well as their use for improving therapeutic precision and patient outcomes.

New research from the Brain Vascular Malformation Consortium (BVMC). This summary is based on a paper published in the journal Biochemistry and Biophysics Reports on August 2, 2025, titled "Common and distinct circulating microRNAs in four neurovascular disorders." Read the paper here. Learn more about BVMC. Transcript: New research from the Brain Vascular Malformation Consortium (BVMC), a research group of the Rare Diseases Clinical Research Network.Comparing Circulating microRNAs in Neurovascular Disorders.This summary is based on a paper published in the journal Biochemistry and Biophysics Reports on August 2, 2025.Familial cerebral cavernous malformations (FCCM), Sturge-Weber syndrome (SWS), and hereditary hemorrhagic telangiectasia (HHT) are neurovascular disorders caused by genetic mutations that can lead to brain bleeding. Cerebral microbleeds (CMBs) are another type of neurovascular disorder that causes brain bleeding. However, CMBs are more often associated with the aging process than genetic factors.In this study, researchers compared circulating microRNAs in these four neurovascular disorders. First, the team identified differentially expressed plasma microRNAs from patients with FCCM, SWS, HHT, and CMB. Next, they used analysis techniques to identify gene targets of the differentially expressed microRNAs and their associated pathways.Results revealed both similarities and differences in microRNAs. Among all four disorders, dysregulated microRNAs targeted the PI3K-Akt and ROBO SLIT signaling pathways. Authors note that these findings reveal shared mechanistic pathways underlying vascular dysmorphism and bleeding, highlighting their potential use for disease monitoring and therapeutic intervention.

New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the journal Nature Immunology on June 26, 2025, titled "Mutations in the human CSF1R gene impact microglia’s maintenance of brain white matter integrity." Read the paper here. Learn more about GLIA-CTN. Transcript: New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN), a research group of the Rare Diseases Clinical Research Network.Examining the Molecular Mechanisms of Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.This summary is based on a paper published in the journal Nature Immunology on June 26, 2025.Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurodegenerative disorder that affects the white matter of the brain. ALSP is caused by mutations in the CSF1R gene, which provides instructions for making a protein called the colony-stimulating factor 1 receptor (CSF1R). This protein plays a crucial role in the growth and survival of immune cells in the brain called microglia. In this study, researchers examined the molecular mechanisms of ALSP. The team performed single-nucleus RNA sequencing on brain specimens with and without ALSP.Results revealed distinctive characteristics of ALSP brains, including significantly lower amounts of microglia and impaired maintenance of brain white matter. Authors note that these findings highlight potential therapeutic strategies for ALSP and other genetically caused microgliopathies.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Frontiers in Immunology on June 17, 2025, titled "Subtype-specific atypical B cell profiles in myasthenia gravis reveal distinct immunopathological pathways." Read the paper here. Learn more about MGNet. Transcript: New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.Exploring the Effect of Atypical B Cells on Immune Response in Myasthenia Gravis. This summary is based on a paper published in the journal Frontiers in Immunology on June 17, 2025.Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChR) in muscles, causing disabling weakness. Subtypes of MG—AChR-positive MG and muscle-specific kinase (MuSK)-positive MG—have different immune responses that may be caused by atypical B cells, an emerging subset of immune cells implicated in autoimmunity.In this study, researchers explored the effect of atypical B cells on immune response in MG. The team used spectral flow cytometry to analyze atypical B cells in individuals with AChR-MG and MuSK-MG as well as healthy controls.Results revealed that MG subtypes show distinct atypical B cell profiles that are linked to immunopathology and disease onset. Authors note that these findings highlight the potential for atypical B cells as therapeutic targets in both immunoglobin G1-3- and immunoglobin G4-mediated autoimmunity.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Neurology Neuroimmunology & Neuroinflammation on July 18, 2025, titled "AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis." Read the paper here. Learn more about MGNet. Transcript: New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.Investigating Pathogenic Properties of Acetylcholine Receptor Autoantibodies in Myasthenia Gravis. This summary is based on a paper published in the journal Neurology Neuroimmunology & Neuroinflammation on July 18, 2025.Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages the neuromuscular junction in muscles, causing disabling weakness with characteristic fluctuation in severity over time. The most common form of MG is caused by acetylcholine receptor (AChR) autoantibodies, which either block the AChR, increase their removal from the muscle surface, or block complement.In this study, researchers investigated the pathogenic properties of AChR autoantibodies in MG and whether they varied over time in relationship to severity of disease. The team analyzed serum specimens from 50 patients with MG collected every six months for two years. Next, they used live cell-based assays to measure AChR autoantibody isotypes, immunoglobulin G subclasses, and the nature of the pathogenic mechanisms.Results showed that the pathogenic mechanisms of the antibodies fluctuated over time and were generally not associated with disease severity. Authors concluded that additional studies of autoantibody pathogenicity should be incorporated into MG clinical trials to assess differential treatment responses.

New research from the Brittle Bone Disorders Consortium (BBDC). This summary is based on a paper published in the journal Families, Systems, and Health on July 10, 2025, titled "Osteogenesis imperfecta and the family: A qualitative analysis of the experiences of family and caregivers." Read the paper here. Learn more about BBDC. Transcript: New research from the Brittle Bone Disorders Consortium (BBDC), a research group of the Rare Diseases Clinical Research Network.Exploring Caregiver Experiences, Social Support, and Impact on Family Life in Osteogenesis Imperfecta.This summary is based on a paper published in the journal Families, Systems, and Health on July 10, 2025.Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Not much is known about the psychosocial impact of OI during childhood on caregivers and families.In this study, researchers explored caregiver experiences, existing social support provided for families affected by OI, and the impact of OI on family life. The team analyzed survey responses from 13 caregivers of individuals with OI to develop themes on the psychosocial impact of OI on the family unit.Results revealed four themes, including encountering difficult experiences during diagnosis of OI, caregiver well-being and coping, broad family impact, and the existence and further need for social support. Authors note that these findings have implications for child and caregiver well-being and health care professionals during diagnosis, as well as emphasize the need for social support for families affected by OI.

New research from the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC). This summary is based on a paper published in the journal Clinical Chemistry on April 25, 2025, titled "Congenital Disorder of Glycosylation in a 40-Year-Old Male with Hypogammaglobulinemia." Read the paper here. Learn more about FCDGC. Transcript: New research from the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC), a research group of the Rare Diseases Clinical Research Network.Diagnosing a New Case of Mannosyl-Oligosaccharide Glucosidase-Congenital Disorder of Glycosylation.This summary is based on a paper published in the journal Clinical Chemistry on April 25, 2025.Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Mannosyl-oligosaccharide glucosidase (MOGS)-CDG is a very rare type of CDG caused by mutations in the MOGS gene.In this journal article, researchers describe the diagnosis of a new case of MOGS-CDG. The 40-year-old male patient presented with symptoms including pan-hypogammaglobulinemia (low immunoglobulin levels). Researchers performed several tests, including an immune genetic disease gene panel and N-glycan analysis. Results confirmed a diagnosis of MOGS-CDG.

New research from the Inherited Neuropathy Consortium (INC). This summary is based on a paper published in the journal Brain on June 9, 2025, titled "Charcot-Marie-Tooth disease type 1E: clinical natural history and molecular impact of PMP22variants." Read the paper here. Learn more about INC. Transcript: New research from the Inherited Neuropathy Consortium (INC), a research group of the Rare Diseases Clinical Research Network.Investigating the Correlation Between Disease Severity and Genetic Variants in Charcot-Marie-Tooth Disease Type 1E.This summary is based on a paper published in the journal Brain on June 9, 2025.  Charcot-Marie-Tooth disease type 1E (CMT1E) is a neuromuscular disorder that affects the peripheral nerves of the feet and hands, leading to neuropathy. Since CMT1E is caused by different kinds of variants in the PMP22 gene, patients can experience a spectrum of mild to severe symptoms. Not much is known about the natural history and symptom progression among these individuals.In this study, researchers investigated the correlation between disease severity and genetic variants in CMT1E. First, the team evaluated patients with CMT1E during initial and follow-up visits at sites within the Inherited Neuropathy Consortium, documenting clinical characteristics and evaluating changes over time. Next, researchers correlated PMP22 variants with disease severity.Results revealed 24 likely disease-causing PMP22 variants among 50 individuals.The team found that reduced expression of PMP22 at the cell surface—and the location of missense variants within the transmembrane domain—correlated with disease severity. In addition, pathogenic PMP22 variants located within the transmembrane regions were often found to cause moderate to severe disease beginning in early childhood, impairing trafficking to the plasma membrane.

New research from the Lysosomal Disease Network (LDN). This summary is based on a paper published in the journal Pediatric Neurology on June 16, 2025, titled "Impact of CLN3 Disease on Child Quality of Life and Family Function." Read the paper here. Learn more about LDN. Transcript: New research from the Lysosomal Disease Network (LDN), a research group of the Rare Diseases Clinical Research Network.Evaluating Health-Related Quality of Life and Family Function in CLN3 Disease.This summary is based on a paper published in the journal Pediatric Neurology on June 16, 2025.CLN3 disease, also known as Batten disease, is an inherited neurodegenerative disorder that typically starts in childhood. Because CLN3 disease is progressive and fatal, it is likely to affect the health-related quality of life (HRQOL) of both the child and the family.In this study, researchers evaluated the HRQOL and family function in individuals with CLN3 disease and their families. The team analyzed data from 71 participants who completed assessments on the child HRQOL and family impact. In 21 of these participants, the team also analyzed Unified Batten Disease Rating Scale responses.Results showed an association between worse child HRQOL and more severe disease symptoms, including physical impairment and functional capability. However, family impact severity was not associated with CLN3 disease symptom severities. While child HRQOL worsened over time, family impact did not significantly change over time. Authors note that these findings may provide important information for clinical care and trial design in CLN3 disease.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the European Journal of Neurology on June 25, 2025, titled "Validation of the 'Patient-Acceptable Symptom State' Question as Outcome Measure in AChR Myasthenia Gravis: A Multicentre, Prospective Study." Read the paper here. Learn more about MGNet. Transcript: New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network.  Validating the Patient-Acceptable Symptom State (PASS) Question in Acetylcholine Receptor Myasthenia Gravis.This summary is based on a paper published in the European Journal of Neurology on June 25, 2025.Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. New treatments have recently emerged for acetylcholine receptor (AChR) antibody-positive MG (AChR-MG). However, not all patients experience significant improvement, highlighting the importance of including the patient perspective in outcome evaluations.In this study, researchers validated the Patient-Acceptable Symptom State (PASS) question as an outcome measure in AChR-MG. The team analyzed PASS responses among 173 patients with AChR-MG.Results confirmed the PASS question as an effective, concise tool to assess AChR-MG patients' satisfaction with their disease control. Authors note that these findings also highlight the relevance of ocular complaints in patients' perception of MG burden.

New research from the Dystonia Coalition (DC). This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on June 18, 2025, titled "Genetic Diversity and Expanded Phenotypes in Dystonia: Insights From Large-Scale Exome Sequencing." Read the paper here. Learn more about DC. Transcript: New research from the Dystonia Coalition (DC), a research group of the Rare Diseases Clinical Research Network.Exploring Genetic Diversity and Phenotypes in Dystonia.This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on June 18, 2025.Dystonia is one of the most prevalent movement disorders, characterized by involuntary muscle contractions leading to abnormal postures and repetitive movements. Due to the broad spectrum of clinical manifestations and the increasing number of dystonia-linked genes, not much is known about the correlations between clinical manifestations and genetic variants.In this study, researchers explored genetic diversity and phenotypes in dystonia. The team used exome sequencing among 1,924 genetically unsolved, mainly late-onset isolated dystonia patients to examine and analyze rare variants in genes previously linked to dystonia.Results revealed 137 pathogenic or likely pathogenic variants across 51 genes in 163 patients. Authors note that the findings provide crucial insights into the relevance of genetic forms of dystonia and their corresponding phenotypes, aiding future variant interpretation and clinical diagnostics.

New research from the Developmental Synaptopathies Consortium (DSC). This summary is based on a paper published in the journal npj Genomic Medicine on May 20, 2025, titled "Genomic diversity in functionally relevant genes modifies neurodevelopmental versus neoplastic risks in individuals with germline PTEN variants." Read the paper here. Learn more about DSC. Transcript: New research from the Developmental Synaptopathies Consortium (DSC), a research group of the Rare Diseases Clinical Research Network.Exploring the Relationship Between Genomic Diversity and Neurodevelopmental Versus Cancer Risks in Individuals with PTEN Hamartoma Tumor Syndrome. This summary is based on a paper published in the journal npj Genomic Medicine on May 20, 2025.PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations in the PTEN gene, which typically suppresses formation of tumors. Individuals with PHTS have increased risks of cancer and neurodevelopmental disorders, including autism spectrum disorder (ASD). Not much is known about why patients with PHTS are at increased risk for these seemingly unrelated outcomes. In this study, researchers explored the relationship between genomic diversity and neurodevelopmental versus cancer risks in individuals with PHTS. The team analyzed the genotypes of 376 individuals with PHTS and grouped them according to clinical phenotypes of neurodevelopmental disorders (including ASD) and non-neurodevelopmental disorders (including cancer).In the neurodevelopmental disorders group, results revealed an increased accumulation of homozygous common variants in genes involved in inflammatory processes. In the ASD group, researchers also found an increased accumulation of homozygous common variants in genes involved in differentiation and chromatin structure regulation. However, in the cancer group, the team found an increased accumulation of homozygous ultra-rare variants in genes modulating cell death.Authors note that these findings suggest a new concept of genomic diversity as a modifier of neurodevelopmental and malignant phenotypes in those with PHTS. Results also demonstrate potential clinical utility—especially for neurodevelopmental phenotypes—for better PHTS patient management.

New research from the Developmental Synaptopathies Consortium (DSC). This summary is based on a paper published in the American Journal of Medical Genetics on June 16, 2025, titled "Genome Sequencing Uncovers Additional Findings in Phelan-McDermid Syndrome." Read the paper here. Learn more about DSC. Transcript: New research from the Developmental Synaptopathies Consortium (DSC), a research group of the Rare Diseases Clinical Research Network.Using Genome Sequencing to Identify Additional Molecular Diagnoses in Phelan-McDermid Syndrome.This summary is based on a paper published in the American Journal of Medical Genetics on June 16, 2025.Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder that results from the loss of a small piece of chromosome 22 or variants in the SHANK3 gene. Symptoms of PMS include intellectual disability, autism spectrum disorder, low muscle tone, and absent speech. However, these symptoms can vary widely from person to person, even among those with the same molecular cause. In this study, researchers used genome sequencing to identify additional molecular diagnoses that may contribute to symptom variability in PMS. The team analyzed genome sequencing and chromosomal microarray in 20 individuals with PMS.Results revealed a second molecular finding associated with a neurological condition in three participants. Five additional new molecular diagnoses were associated with a clinically actionable secondary or incidental finding. Authors note that this study provides early evidence for the potential use of expanded sequencing among individuals with PMS, even for those without symptoms outside of the expected range.

New research from the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC). This summary is based on a paper published in the journal Cells on April 25, 2025, titled "Complex Metabolomic Changes in a Combined Defect of Glycosylation and Oxidative Phosphorylation in a Patient with Pathogenic Variants in PGM1 and NDUFA13." Read the paper here. Learn more about FCDGC. Transcript: New research from the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC), a research group of the Rare Diseases Clinical Research Network.Examining Metabolomic Changes in a Patient with PGM1-Congenital Disorder of Glycosylation and Leigh Syndrome.This summary is based on a paper published in the journal Cells on April 25, 2025.Inherited metabolic disorders (IMDs) are a large group of genetically inherited disorders that affect the metabolism. Although there are currently about 1,450 different types of IMDs, they are individually rare, and even more rare for one individual to have two IMDs.In this study, researchers examined metabolism changes in a patient with pathogenic variants in the PGM1 and NDUFA13 genes. The team evaluated fibroblasts from the patient, who had presented with characteristics of both PGM1-congenital disorder of glycosylation (CDG) and Leigh syndrome (mitochondrial disease) to better understand the cause of these characteristics. Results showed a depletion of the UDP-hexose enzyme as well as impairment of complex I enzyme activity and mitochondrial function. Based on these findings, the patient was diagnosed with the first-known case of both PGM1-CDG and Leigh syndrome. Authors note that this study underlines the importance of considering the effects of multiple disease-causing variants in patients with complex clinical presentation.

New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the Journal of Inherited Metabolic Disease on June 2, 2025, titled "Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data Approach." Read the paper here. Learn more about GLIA-CTN. Transcript: New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN), a research group of the Rare Diseases Clinical Research Network.Characterizing Diagnostic Delays in Metachromatic Leukodystrophy.This summary is based on a paper published in the Journal of Inherited Metabolic Disease on June 2, 2025.Metachromatic leukodystrophy (MLD) is a rare inherited disorder that causes progressive damage to the nervous system. The subtypes of MLD are defined by the onset of neurodegeneration, but less is known about the earliest features of this inborn error in metabolism. In this study, researchers found that many children experience subtle early features in the months to years prior to diagnosis. The early medical journeys of children were mapped using two independent payor-system databases. Every medical encounter prior to diagnosis was captured. Across these cohorts, they found that children frequently presented within the medical system with signs and symptoms of disease, including early developmental delay, feeding issues, gallbladder problems, and abnormal eye movements. This work was complemented by similar findings from an MLD natural history study, which is supported through the GLIA-CTN. Authors note that this study highlights early features of MLD and defines barriers to diagnosis, further supporting the need for early screening. By better understanding the barriers to diagnosis and characterizing how MLD begins, we can better define clinical monitoring guidelines in presymptomatic children and define ideal windows for intervention to improve outcomes. This work underscores the critical need for newborn screening to definitively diagnose children prior to disease onset.

New research from the Myasthenia Gravis Rare Disease Network (MGNet). This summary is based on a paper published in the journal Muscle & Nerve on April 2, 2025, titled "Concordance between radioimmunoassay and fixed cell-based assay in subjects without myasthenia gravis: optimizing the diagnostic approach." Read the paper here. Learn more about MGNet. Transcript:New research from the Myasthenia Gravis Rare Disease Network (MGNet), a research group of the Rare Diseases Clinical Research Network. Developing an Artificial Intelligence-Based Assessment of Telehealth Examinations in Myasthenia Gravis. This summary is based on a paper published in the journal Muscle & Nerve on April 2, 2025.  Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Although telemedicine is considered a positive tool for both MG patients and physicians, not much is known about its strengths and limitations for MG examinations.In this study, researchers developed an artificial intelligence-based assessment of telehealth examinations in MG. The team studied video recordings of 51 patients with MG who completed two telemedicine-based examinations with neuromuscular experts. Researchers applied artificial intelligence algorithms including computer vision, speech analysis, and natural language processing to assess the reproducibility and reliability of the examinations.Results showed that overall MG core examination scores were consistent across examiners. However, individual metrics showed up to 25% variability due to differences in examiner instructions, video recording limitations, and patient disease severity. Authors note that further refinement of this technology could enhance examiner training and reduce variability in clinical trial outcome measures.