Rare Research Report

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Rare Research Report features summaries of recent scientific publications from the Rare Diseases Clinical Research Network, which is funded by the National Institutes of Health. The network includes 20 active consortia—teams of researchers, patients, and clinicians—each focused on a group of rare disorders. Join us for new episodes each month. Learn more about the RDCRN: https://www.rarediseasesnetwork.org

  1. MAR 27

    GLIA-CTN: Investigating Language Skills in Children with Alexander Disease

    New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the American Journal of Speech-Language Pathology on January 13, 2026, titled "Language Skills in Patients With Alexander Disease." 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. Investigating Language Skills in Children with Alexander Disease. This summary is based on a paper published in the American Journal of Speech-Language Pathology on January 13, 2026. Alexander disease is a rare disorder of the nervous system characterized as a leukodystrophy, a group of disorders affecting the myelin (the fatty coating surrounding nerve fibers). People with Alexander disease may have trouble walking, speaking, and swallowing. In this study, researchers investigated the relationship between disease characteristics, age, and language skills in patients with Alexander disease. First, the team used clinical and imaging features to determine disease subtypes—including cerebral, intermediate, and bulbospinal—among 82 participants. Next, they used developmentally appropriate tests to assess participants' language and functional communication abilities. Then, they used statistical methods to find differences across groups. Results showed that overall, cerebral patients experienced the most significant language deficits compared to intermediate and bulbospinal patients. Authors note that these findings can be used to better understand the impact of communication deficits and to provide accommodations and interventions in treatment plans for patients with Alexander disease.

    2 min

  2. MAR 27

    SP-CERN: Evaluating the Use of Genome Sequencing in Diagnosing Children with Progressive Movement Disorders

    New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN). This summary is based on a paper published in the journal Brain on February 5, 2026, titled "Diagnostic yield of genome sequencing in children with progressive movement disorders."  Read the paper here.  Learn more about SP-CERN.  Transcript:  New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN), a research group of the Rare Diseases Clinical Research Network. Evaluating the Use of Genome Sequencing in Diagnosing Children with Progressive Movement Disorders. This summary is based on a paper published in the journal Brain on February 5, 2026. Childhood-onset movement disorders have a large range of symptoms and genetic causes. Over 500 different genes are associated with these disorders. However, standard genetic testing may not detect some of the genetic variants. In this study, researchers evaluated the use of genome sequencing in diagnosing children with progressive movement disorders. First, the team used whole genome sequencing to identify variants in 100 children and young adults with early-onset progressive movement disorders and prior nondiagnostic testing. Then, a multidisciplinary team interpreted the variants and matched them with different phenotypes. Results included a molecular diagnosis in 27% of cases, with candidate variants identified in an additional 33%. Short-read whole genome sequencing showed a small increase in diagnoses over exome sequencing. Most of the diagnoses were achieved through reanalysis of exome-level data. Authors note that these findings highlight the importance of repeat variant interpretation and the need for improved analytic pipelines to fully realize the potential of genome sequencing.

    2 min

  3. FEB 24

    GLIA-CTN: Exploring the Use of Glial Fibrillary Acidic Protein as a Biomarker in Alexander Disease

    New research from the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN). This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on January 9, 2026, titled "Characterization of Clinical Phenotype to Glial Fibrillary Acidic Protein Concentrations in Alexander Disease." 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. Exploring the Use of Glial Fibrillary Acidic Protein as a Biomarker in Alexander Disease. This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on January 9, 2026. Alexander disease is a rare disorder of the nervous system characterized by leukodystrophy, or the destruction of myelin (the fatty coating surrounding nerve fibers). In patients with Alexander disease, variants in the GFAP gene lead to the buildup of glial fibrillary acidic protein (GFAP) in the body. Not much is known about the relationship between GFAP levels and disease characteristics.  In this study, researchers explored the use of GFAP as a biomarker in Alexander disease. First, the team collected cerebrospinal fluid and plasma from participants with and without Alexander disease. Next, they compared the concentration of GFAP over time between these groups, including those with common disease characteristics or genetic variants. Results showed that GFAP increases over time in young children with Alexander disease. The highest concentrations of GFAP were seen in those with the cerebral disease type. Authors note that these findings are a critical initial step in defining biomarker validation and context of use for GFAP in Alexander disease.

    2 min

  4. FEB 24

    GLIA-CTN: Reviewing Pathology and Interventions in Cerebral X-Linked Adrenoleukodystrophy

    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 February 2026 titled "Inflammation and Immunomodulation in Cerebral X-linked Adrenoleukodystrophy: Review of Pathology and Interventions." 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. Reviewing Pathology and Interventions in Cerebral X-Linked Adrenoleukodystrophy. This summary is based on a paper published in the Journal of Child Neurology in February 2026. X-linked adrenoleukodystrophy (ALD) is a disorder on the X chromosome characterized by the disruption in fat metabolism (break down) which leads to the accumulation of long-chain fatty acids throughout the nervous system, adrenal glands, and testes. More than half of male patients with ALD develop progressive, inflammatory cerebral demyelination (loss of the fatty coating surrounding nerves). Treatment for cerebral ALD is limited, with no standard therapies available for the advanced form. In this study, researchers reviewed pathology and interventions in cerebral X-linked ALD. The review included over 50 years of published literature and expert opinion from clinicians caring for patients around the world. From these sources, the team gathered information on immunopathology, biomarkers, and therapies tested. Findings revealed insights on inflammation and immunomodulation in cerebral X-linked ALD. Authors note that these findings highlight the potential of a future clinical trial of immunomodulatory agents for advanced cerebral ALD.

    2 min

  5. FEB 24

    NAMDC: Using a New Statistical Technique for Accelerometer Data to Assess a Treatment for Mitochondrial Disease

    New research from the North American Mitochondrial Disease Consortium (NAMDC). This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology in December 2025 titled "Assessing a Mitochondrial Disease Treatment via a Novel Statistical Technique for Accelerometer Data."  Read the paper here.  Learn more about NAMDC.  Transcript:  New research from the North American Mitochondrial Disease Consortium (NAMDC), a research group of the Rare Diseases Clinical Research Network. Using a New Statistical Technique for Accelerometer Data to Assess a Treatment for Mitochondrial Disease. This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology in December 2025. Mitochondrial diseases are multisystemic, genetic disorders involving dysfunction of the mitochondria (specialized cell structures that produce energy), which affects cellular metabolism. Development of new therapies for mitochondrial diseases is difficult due to a lack of outcome measures. In this study, researchers used a new statistical technique for accelerometer data to assess a treatment for mitochondrial disease. First, the team collected data over several clinic visits from 14 patients with thymidine kinase 2 deficiency (TK2d), an ultra-rare autosomal recessive mitochondrial disease, in a clinical trial for nucleoside therapy. Next, the team used a combination of functional data analysis and longitudinal mixed-effects linear regression to compare accelerometer data over the course of treatment. Results showed that nucleoside therapy resulted in significant improvement in activity levels among TK2d patients. Authors note that these findings could reveal a possible primary outcome biomarker in clinical trials for mitochondrial diseases as well as other types of diseases, both rare and common.

    2 min

  6. FEB 24

    SP-CERN: Assessing Health-Related Quality of Life in Children with Rare Forms of Hereditary Spastic Paraplegia

    New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN). This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on November 6, 2025, titled "Health-Related Quality of Life in Rare Forms of Childhood-Onset Hereditary Spastic Paraplegia."  Read the paper here.  Learn more about SP-CERN.  Transcript:  New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN), a research group of the Rare Diseases Clinical Research Network. Assessing Health-Related Quality of Life in Children with Rare Forms of Hereditary Spastic Paraplegia. This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on November 6, 2025. Hereditary spastic paraplegia (HSP) is a large group of inherited disorders that affect nerves that send messages to the muscles. Patients with HSP commonly have difficulty walking due to muscle weakness and spasticity (muscle rigidity) in the legs. In patients with rare forms of HSP, these symptoms can be more complex, including developmental delay, intellectual disability, movement disorders, dysphagia (difficulty swallowing), or incontinence. While previous studies have examined how common forms of HSP affect health-related quality of life, less is known about the impact of rare childhood-onset forms. In this study, researchers assessed health-related quality of life in 80 children with rare forms of HSP. Using the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) and clinician-reported outcomes, the team examined how clinical features, age, and genotype correlate with quality of life. Results showed that CPCHILD can be used to assess many different forms of childhood-onset HSP. Lower scores were seen in children with more complex forms. Motor, autonomic, and bulbar symptoms had the largest impact. Authors note that these insights can help clinicians prioritize interventions and inform strategies to improve quality of life for children with HSP.

    2 min

  7. FEB 24

    SP-CERN: Investigating the ATG9A Ratio as a Diagnostic Tool for Adaptor Protein Complex 4–Associated Hereditary Spastic Paraplegia

    New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN). This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on January 5, 2026, titled "Diagnostic Utility of the ATG9A Ratio in AP-4–Associated Hereditary Spastic Paraplegia."  Read the paper here.  Learn more about SP-CERN.  Transcript:  New research from the Spastic Paraplegia Centers of Excellence Research Network (SP-CERN), a research group of the Rare Diseases Clinical Research Network. Investigating the ATG9A Ratio as a Diagnostic Tool for Adaptor Protein Complex 4–Associated Hereditary Spastic Paraplegia.  This summary is based on a paper published in the journal Annals of Clinical and Translational Neurology on January 5, 2026.   Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders that cause the upper motor neurons to slowly degenerate, leading to progressive muscle stiffness and leg weakness. Adaptor protein complex 4–associated HSP (AP-4-HSP) is a childhood-onset and complex form of HSP that causes mislocalization—buildup in the wrong location—of the protein ATG9A. Gradual progression of initial symptoms, similarity with other developmental conditions like cerebral palsy, and unknown significance of genetic variants can make it challenging to diagnose AP-4-HSP. In this study, researchers investigated the ATG9A ratio as a diagnostic tool for AP-4-HSP. The team measured the mislocalization of ATG9A in eight patients with suspected AP-4-HSP and genetic variants of unknown significance. Results demonstrated loss of AP-4 function in six of the participants, revealing new disease-causing genetic variants. Authors note that the ATG9A ratio is a useful tool for diagnosing AP-4-HSP and classifying new genetic variants, which can help determine eligibility for clinical trials and guide treatment decisions.

    2 min

  8. FEB 24

    UCDC: Evaluating a New Food Photography App for Measuring Dietary Intake in Urea Cycle Disorders

    New research from the Urea Cycle Disorders Consortium (UCDC). This summary is based on a paper published in the journal Molecular Genetics and Metabolism in December 2025 titled "Measuring dietary intake among participants with a urea cycle disorder using standard diet records or a novel food photography app."  Read the paper here.  Learn more about UCDC.  Transcript:  New research from the Urea Cycle Disorders Consortium (UCDC), a research group of the Rare Diseases Clinical Research Network. Evaluating a New Food Photography App for Measuring Dietary Intake in Urea Cycle Disorders. This summary is based on a paper published in the journal Molecular Genetics and Metabolism in December 2025. Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Nutrition management can help prevent hyperammonemia by limiting protein intake while providing enough energy for growth. However, traditional methods of assessing dietary intake—including three-day diet records, 24-hour recalls, and food frequency questionnaires—are often time-consuming and inaccurate. In this study, researchers evaluated a new food photography app for measuring dietary intake in individuals with UCDs. Eight participants used the new app, mFood, to take photos of meals and snacks for remote analysis by a registered dietician. The team then compared the accuracy of mFood with traditional three-day diet records. Results revealed few statistical differences between mFood and traditional methods. However, the majority of participants preferred using mFood, offering a more convenient way for individuals with UCDs to collect nutrition information.

    2 min
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About

Rare Research Report features summaries of recent scientific publications from the Rare Diseases Clinical Research Network, which is funded by the National Institutes of Health. The network includes 20 active consortia—teams of researchers, patients, and clinicians—each focused on a group of rare disorders. Join us for new episodes each month. Learn more about the RDCRN: https://www.rarediseasesnetwork.org

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  • Creator
    RDCRN
  • Years Active
    2022 - 2026
  • Episodes
    199
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    Clean
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    © Copyright RDCRN
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