Orphanet Journal of Rare Diseases

ObjectiveA phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP-004 (5-aminolevulinic acid hydrochloride and sodium ferrous citrate) in patients diagnosed as Leigh syndrome (LS) was conducted to confirm the efficacy and safety of SPP-004 in patients with LS showing central nervous system disorders. MethodsFifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients showing improved scores on the Newcastle Paediatric Mitoch...

PurposeSuccessful transition to adulthood requires intact executive and adaptive function. These neurocognitive domains, critical for independence, are frequently impaired in inherited metabolic disorders (IMD), though predictive clinical and biochemical factors are lacking. Standardized assessments linking neurocognitive status with functional outcomes are needed to improve prognostication and tailor support for affected emerging adults. MethodsMaple Syrup Urine Disease (MSUD), a relatively pr...

Neurofibromatosis type 1 (NF1) is a common genetic condition in which 30-70% of children experience learning challenges including deficits in attention, executive function, and working memory. White matter pathways have been implicated in these cognitive functions; yet, they have not been well characterized in NF1. In this retrospective cohort study, we used diffusion MRI tractography to examine the microstructural properties of major white matter pathways in 20 children with NF1 aged 1 year to ...

ObjectiveA multi-center, prospective, cross-sectional natural history study to define the clinical phenotype of Andersen-Tawil syndrome, validate its current diagnostic criteria, explore genotype-phenotype correlations, and establish clinically relevant endpoints for use in therapeutic trials. MethodsParticipants were followed at yearly intervals for two years. Outcome measures included attack frequency and duration, neurophysiological exercise testing and interictal muscle strength. Cardiac en...

Background and aimsChronic pain is a major part of the disease burden in Charcot-Marie-Tooth (CMT) disease. Current pharmacotherapies to manage symptoms of CMT disease, particularly pain, are inadequate. This exploratory study examined the patient reported efficacy of medical cannabis among CMT patients. MethodsParticipants (N = 56; 71.4% female; Age = 48.9, SD = 14.6; 48.5% CMT1) were recruited though the Hereditary Neuropathy Foundations Global Registry for Inherited Neuropathies. The online ...

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we include...

BackgroundIntraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique. MethodsWe conducte...

There are many causes for cervical dystonia (CD), although most cases are idiopathic and a cause cannot be identified. The observation that 10-15% of cases have an affected family member has pointed to genetic causes, but known genes account for only a small fraction of all cases. The current manuscript describes a series of studies focusing on potential autoimmune or inflammatory mechanisms in CD. First, a case-control survey for 32 autoimmune diseases in 271 subjects with CD confirmed prior an...

In LGMDR1-Calpain-3 related, as in all muscular dystrophies, clinical trial monitoring remains a challenge due to the lack of reliable biomarkers. This study assessed IL-32 concentrations in both serum and urine, uncovering a marked increase in patients compared to healthy controls. Serum IL-32 levels were especially elevated in young adults, suggesting a possible link to the early and more active phases of disease onset. Meanwhile, urinary IL-32 levels showed consistent elevation across all age...

ObjectiveTo investigate the association of visual impairment (VI) with brain structures in the UK Biobank Study. MethodsThe UK Biobank Study is a large prospective study that recruited more than 500,000 participants aged 40-69 from 2006 to 2010 across the UK. Visual acuity (VA) of worse than 0.3 LogMAR units (Snellen 20/40) was defined as VI. Structural magnetic resonance imaging (MRI) data were obtained using a 3.0-T MRI imager. Volumetric measures of five global brain volumes (total brain vol...

BackgroundAberrant myelination represents a critical but understudied mechanism in cognitive difficulties associated with neurodevelopmental conditions. Neurofibromatosis 1 (NF1), provides a unique monogenic model to investigate this relationship, as white matter abnormalities are consistently observed, yet their microstructural basis remains uncharacterized. We present the first dual-modality quantitative myelin mapping study in NF1, employing Magnetization Transfer and T1W/T2W ratio imaging to...

BackgroundLong COVID (LC) is a novel condition that is characterized by persistent symptoms that last from months to years following a SARS-CoV-2 infection. While LC symptoms vary widely, neuropathy is one of the most prevalent symptoms and drastically affects patients quality of life. However, the underlying pathophysiology of LC neuropathy remains poorly understood. Here, we investigated the prevalence and potential mechanisms of LC neuropathy in the largest LC neuropathy cohort to date. Meth...

ObjectiveThe primary objective of this study was to inform and assist in planning the design of a patient navigator randomized controlled trial. We explored patient perceptions and preferences for the proposed intervention and their broader care experiences with diabetic foot ulcer (DFU) care. We additionally conducted a retrospective chart review to investigate if patient navigator phone calls are associated with increased clinic attendance and a pilot study of a 30-day post discharge navigator...

There is currently no FDA approved treatment for Batten disease CLN1, a rapidly progressive, fatal, and rare pediatric neurodegenerative disease. In this article, we aimed to collect retrospective clinical data from the families to identify CLN1 patients for a future patient facing natural history study and clinical trial. We have therefore developed and launched an institutional review board approved Batten disease CLN1 registry (https://cln1registry.collaborationspharma.com). We implemented a ...

BackgroundNeurofibromatosis-1 (NF1) is an autosomal dominant neurodevelopmental condition commonly characterised by learning difficulties, with co-occurring autism spectrum conditions in 30% and attention deficit hyperactivity disorder in about 50% of affected school-age children. The structural brain phenotype characteristically shows T2-white matter hyperintensities, particularly in the thalamus and basal ganglia, and previous diffusion MRI studies have demonstrated widespread white matter mic...

ObjectivesObservational studies have shown the association between knee osteoarthritis (KOA) and neurological disorders with alterations in brain imaging-derived phenotypes (BIDPs). This study aimed at investigating whether alterations in brain structure are correlated with the occurrence of KOA. MethodsBased on the summary data from two large scale genome-wide association studies (GWASs), we performed a bidirectional two-sample Mendelian randomization (MR) analysis using single-nucleotide poly...

PurposePerinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. MaterialWe studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifi...

ObjectiveGenetic testing practices are rapidly evolving for people living with, or at-risk for, amyotrophic lateral sclerosis (ALS), due to emerging genotype-driven therapies. This study explored how individuals at-risk for familial ALS (fALS) perceive the opportunity to participate in a clinical trial, and to better understand how that may influence the decision-making process for predictive genetic testing. MethodsThis study used both quantitative and qualitative data analyses. Data were coll...

BackgroundSarcoglycanopathies (SG) is the most frequent form of autosomal recessive limb-girdle muscular dystrophies (LGMD) leading to progressive muscle wasting and weakness, predominantly characterized by limb-girdle weakness. LGMDR4 is caused by mutations in SGCB encoding for the beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype cosegregating in 14 SG cases from 13 unrelated families with the likely pathogenic homozygous mutation c.544A>C (p.Thr182Pro) in SGCB. ...

BackgroundSpinocerebellar ataxia-36 (SCA36) is an inherited neurodegenerative disorder caused by the heterozygous expansion of an intronic GGCCTG hexanucleotide repeat in the NOP56 gene on chromosome 20p13. Unaffected individuals typically carry 3 to 14 repeats, whereas affected individuals carry 650 to 2,500. However, based on a single study, this pathogenic range was conservatively established, limiting its extended clinical applicability such as preimplantation genetic testing (PGT). In this ...