FASEB J. 2024 Mar 15;38(5):e23536. doi: 10.1096/fj.202302259RR.

ABSTRACT

Rituximab, the first monoclonal antibody approved for the treatment of lymphoma, eventually became one of the most popular and versatile drugs ever in terms of clinical application and revenue. Since its patent expiration, and consequently, the loss of exclusivity of the original biologic, its repurposing as an off-label drug has increased dramatically, propelled by the development and commercialization of its many biosimilars. Currently, rituximab is prescribed worldwide to treat a vast range of autoimmune diseases mediated by B cells. Here, we present a comprehensive overview of rituximab repurposing in 115 autoimmune diseases across 17 medical specialties, sourced from over 1530 publications. Our work highlights the extent of its off-label use and clinical benefits, underlining the success of rituximab repurposing for both common and orphan immune-related diseases. We discuss the scientific mechanism associated with its clinical efficacy and provide additional indications for which rituximab could be investigated. Our study presents rituximab as a flagship example of drug repurposing owing to its central role in targeting cluster of differentiate 20 positive (CD20) B cells in 115 autoimmune diseases.

PMID:38470360 | DOI:10.1096/fj.202302259RR

Orphanet J Rare Dis. 2024 Mar 11;19(1):112. doi: 10.1186/s13023-024-03120-1.

ABSTRACT

BACKGROUND: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers.

RESULTS: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston in 2021 to create a new version of the TSRR that completely separates participant health data (stored at UTHealth) and personal identifiers (maintained at TSSUS). We developed an innovative Visual Basic (VB) script that, when embedded into Microsoft Outlook, redirects REDCap surveys through TSSUS to participants by matching registry IDs to participant email addresses. Additionally, the utilization of REDCap allows for portability of data as it is an open source platform.

CONCLUSION: In this report, we will highlight three recent changes that more closely align the TSRR with this mission: a unique and equal collaborative partnership between UTHealth and TSSUS, an open-source platform, REDCap, that ensures data portability and compatibility across institutions, and an innovative survey routing system that retains participant confidentiality without sacrificing REDCap survey distribution capabilities to connect researchers with thousands of participants.

PMID:38468317 | PMC:PMC10929126 | DOI:10.1186/s13023-024-03120-1

bioRxiv [Preprint]. 2024 Feb 26:2024.02.26.581979. doi: 10.1101/2024.02.26.581979.

ABSTRACT

SELENON-Related Myopathy (SELENON-RM) is a rare congenital myopathy caused by mutations of the SELENON gene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology commonly includes multiminicores or a dystrophic pattern but is often non-specific. The SELENON gene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency causes SELENON-RM are undetermined. A hurdle is the lack of cellular and animal models that show assayable phenotypes. Here we report deep-phenotyping of SelN-deficient zebrafish and muscle cells. SelN-deficient zebrafish exhibit changes in embryonic muscle function and swimming activity in larvae. Analysis of single cell RNAseq data in a zebrafish embryo-atlas revealed coexpression between selenon and genes involved in glutathione redox pathway. SelN-deficient zebrafish and mouse myoblasts exhibit changes in glutathione and redox homeostasis, suggesting a direct relationship with SelN function. We report changes in metabolic function abnormalities in SelN-null myotubes when compared to WT. These results suggest that SelN has functional roles during zebrafish early development and myoblast metabolism.

PMID:38464009 | PMC:PMC10925121 | DOI:10.1101/2024.02.26.581979

Orphanet J Rare Dis. 2024 Mar 7;19(1):104. doi: 10.1186/s13023-024-03112-1.

ABSTRACT

BACKGROUND: Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked metabolic disorder predominantly affecting males. Pabinafusp alfa, an iduronate-2-sulfatase enzyme designed to cross the blood-brain barrier, was approved in Japan in 2021 as the first enzyme replacement therapy targeting both the neuropathic and somatic signs and symptoms of MPS II. This study reports caregivers' experiences of MPS II patients receiving pabinafusp alfa through qualitative interviews.

METHODS: Semi-structured, qualitative interviews were conducted with caregivers at seven clinical sites in Japan using a semi-structured moderation guide (Voice of the Caregiver guide). Thematic analysis was applied to the interview transcripts to identify symptoms and health-related quality of life impacts at baseline, changes during treatment, and overall treatment experience.

RESULTS: Seven caregivers from 16 trial sites participated, representing seven children aged 8-18 years who had received pabinafusp alfa for 3.3-3.5 years at the time of the interviews. Data suggest a general trend toward improvement in multiple aspects, although not all caregivers observed discernible changes. Reported cognitive improvements included language skills, concentration, self-control, eye contact, mental clarity, concept understanding, following instructions, and expressing personal needs. Further changes were reported that included musculoskeletal improvements and such somatic changes as motor function, mobility, organ involvement, joint mobility, sleep patterns, and fatigue. Four caregivers reported improvements in family quality of life, five expressed treatment satisfaction, and all seven indicated a strong willingness to continue treatment of their children with pabinafusp alfa.

CONCLUSION: Caregivers' perspectives in this study demonstrate treatment satisfaction and improvement in various aspects of quality of life following therapy with pabinafusp alfa. These findings enhance understanding of pabinafusp alfa's potential benefits in treating MPS II and contribute to defining MPS II-specific outcome measures for future clinical trials.

PMID:38454486 | PMC:PMC10921713 | DOI:10.1186/s13023-024-03112-1

An Sist Sanit Navar. 2024 Mar 7;47(1):e1069. doi: 10.23938/ASSN.1069.

ABSTRACT

Catamenial pneumothorax is a spontaneous recurrent pneumothorax that occurs in women of reproductive age and in temporal relationship with the menses. It usually occurs within 24 hours before or 72 hours after the start of the menstrual cycle; however, multiple variations have been described in terms of the temporal relationship. To date, it is considered a rare condition; this may be justified by the limited available knowledge on this disease leading to misdiagnosis. Often, making a diagnosis of catamenial pneumothorax is complicated; it mainly depends on the medical history; also, it may be a surgical or histopathological diagnosis. Management strategies for catamenial pneumothorax may include combinations of hormonal therapy, pleurodesis, lung parenchyma resection, and diaphragm resection/repair. The aim of reporting this atypical case of catamenial pneumothorax is to highlight the relevance of having the adequate knowledge on this entity so it does not go unnoticed despite its apparent low incidence.

PMID:38451043 | DOI:10.23938/ASSN.1069

IJID Reg. 2024 Feb 22;10:228-234. doi: 10.1016/j.ijregi.2024.02.003. eCollection 2024 Mar.

ABSTRACT

OBJECTIVES: Hepatitis delta virus (HDV) infection has been granted orphan disease status by the US Food and Drug Administration and the European Medicines Agency owing to its rarity and relatively limited research and treatment options. Turkey is considered an endemic country for the virus. We aimed to provide a current and updated country- and region-specific HDV infection prevalence.

METHODS: In this meta-analysis, we searched databases, including MEDLINE, PUBMED, EMBASE, and UlakBim (Turkish Medical Index) published between January 1, 2006, and December 31, 2022. We included blood donor studies, outpatient clinic studies that comprised patients without cirrhosis, and inpatient clinical studies that comprised patients with cirrhosis. Turkey was divided into three regions: West, Central, and East Turkey.

RESULTS: After a systematic assessment, 41 studies were included. Using a random-effects model, the estimated HDV prevalence among hepatitis B surface antigen-positive blood donors, outpatient clinic, and inpatient clinic patients were 3.37% (confidence interval [CI] 1.99-6.11), 5.05% (CI 4.00-6.23), and 29.06% (CI 10.45-51.79), respectively. The HDV prevalence among outpatient clinic patients in Western, Central, and Eastern regions were 3.38% (CI 2.47-4.44), 2.15% (CI 1.37-3.09), and 9.81% (CI 6.61-13.55), respectively.

CONCLUSIONS: East Turkey continues to have a high burden of HDV. Public health efforts, such as screening, should be targeted accordingly.

PMID:38444561 | PMC:PMC10912444 | DOI:10.1016/j.ijregi.2024.02.003

BMC Health Serv Res. 2024 Mar 5;24(1):276. doi: 10.1186/s12913-024-10786-7.

ABSTRACT

BACKGROUND: Economic sanctions aim to exert pressure on political and economic foundations. Hypothesizing that sanctions might affect various aspects of population health, this study, as a component of a broader investigation to ascertain the trend effects of sanctions on selected health outcomes in Iran, seeks to explore the experiences of Iranian citizens associated with the imposed sanctions.

METHODS: This is a qualitative study. We conducted 31 semi-structured interviews with randomly selected patients diagnosed with at least one chronic and rare disease from diverse backgrounds across four provinces in Iran. We analyzed data using an inductive content analysis approach, facilitated by the MAXQDA10 software.

RESULTS: We identified three primary themes: direct effects, side effects, and coping strategies. The immediate effects were perceived to be manifested through the restriction of healthcare service availability and affordability for citizens. The side effects included the economic hardships experienced in individuals' lives and the perceived devastation caused by these difficulties. Some coping mechanisms adopted by patients or their families/relatives included prioritizing comorbidities, prioritizing health needs within families with multiple ill members, and readjusting health/illness requirements in light of daily living needs.

CONCLUSION: In addition to the inherent burden of their illness, patients faced substantial healthcare costs as a result of sanctions, restricted access to medications, and availability of low-quality medications. We advocate considering these challenges within the healthcare system resilience framework as a crucial first step for policymakers, aiming to determine actionable measures and mitigate the adverse effects of sanctions on citizens, particularly the most vulnerable groups.

PMID:38444030 | DOI:10.1186/s12913-024-10786-7

Lancet Diabetes Endocrinol. 2024 Apr;12(4):219-221. doi: 10.1016/S2213-8587(24)00065-2. Epub 2024 Mar 1.

NO ABSTRACT

PMID:38437851 | DOI:10.1016/S2213-8587(24)00065-2

Clin Exp Rheumatol. 2024 Feb;42(2):207-212. doi: 10.55563/clinexprheumatol/hc1lsf. Epub 2024 Mar 4.

ABSTRACT

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

PMID:38436382 | DOI:10.55563/clinexprheumatol/hc1lsf

Health Aff (Millwood). 2024 Mar;43(3):452-455. doi: 10.1377/hlthaff.2023.01001.

ABSTRACT

A mother shares the story of her son's rare disease diagnostic journey and how providers failed them both along the way.

PMID:38437605 | DOI:10.1377/hlthaff.2023.01001

F1000Res. 2023 Aug 30;9:1196. doi: 10.12688/f1000research.26689.2. eCollection 2020.

ABSTRACT

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families.

PMID:38435080 | PMC:PMC10905007 | DOI:10.12688/f1000research.26689.2

Probl Endokrinol (Mosk). 2024 Feb 28;70(1):30-37. doi: 10.14341/probl13321.

ABSTRACT

Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.

PMID:38433539 | DOI:10.14341/probl13321

Eur J Med Genet. 2024 Apr;68:104925. doi: 10.1016/j.ejmg.2024.104925. Epub 2024 Mar 1.

ABSTRACT

PURPOSE: Exome sequencing (ES) and genome sequencing (GS) are diagnostic tests for rare genetic diseases. Studies report clinical utility of ES/GS. The goal of this systematic review is to establish how clinical utility is defined and measured in studies evaluating the impacts of ES/GS results for pediatric patients.

METHODS: Relevant articles were identified in PubMed, Medline, Embase, and Web of Science. Eligible studies assessed clinical utility of ES/GS for pediatric patients published before 2021. Other relevant articles were added based on articles' references. Articles were coded to assess definitions and measures of clinical utility.

RESULTS: Of 1346 articles, 83 articles met eligibility criteria. Clinical utility was not clearly defined in 19% of studies and 92% did not use an explicit measure of clinical utility. When present, definitions of clinical utility diverged from recommended definitions and varied greatly, from narrow (diagnostic yield of ES/GS) to broad (including decisions about withdrawal of care/palliative care and/or impacts on other family members).

CONCLUSION: Clinical utility is used to guide policy and practice decisions about test use. The lack of a standard definition of clinical utility of ES/GS may lead to under- or overestimations of clinical utility, complicating policymaking and raising ethical issues.

PMID:38432472 | DOI:10.1016/j.ejmg.2024.104925

BMC Med Inform Decis Mak. 2024 Mar 3;22(Suppl 2):348. doi: 10.1186/s12911-024-02420-7.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW).

METHODS: We developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC).

RESULTS: Our best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm.

CONCLUSION: Our NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.

PMID:38433189 | PMC:PMC10910523 | DOI:10.1186/s12911-024-02420-7

Orphanet J Rare Dis. 2024 Mar 2;19(1):96. doi: 10.1186/s13023-024-03103-2.

ABSTRACT

BACKGROUND: The conduct of rare disease clinical trials is still hampered by methodological problems. The number of patients suffering from a rare condition is variable, but may be very small and unfortunately statistical problems for small and finite populations have received less consideration. This paper describes the outline of the iSTORE project, its ambitions, and its methodological approaches.

METHODS: In very small populations, methodological challenges exacerbate. iSTORE's ambition is to develop a comprehensive perspective on natural history course modelling through multiple endpoint methodologies, subgroup similarity identification, and improving level of evidence.

RESULTS: The methodological approaches cover methods for sound scientific modeling of natural history course data, showing similarity between subgroups, defining, and analyzing multiple endpoints and quantifying the level of evidence in multiple endpoint trials that are often hampered by bias.

CONCLUSION: Through its expected results, iSTORE will contribute to the rare diseases research field by providing an approach to better inform about and thus being able to plan a clinical trial. The methodological derivations can be synchronized and transferability will be outlined.

PMID:38431612 | DOI:10.1186/s13023-024-03103-2

Nat Genet. 2024 Mar 1. doi: 10.1038/s41588-023-01651-0. Online ahead of print.

ABSTRACT

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.

PMID:38429495 | DOI:10.1038/s41588-023-01651-0

Epilepsia Open. 2024 Mar 1. doi: 10.1002/epi4.12923. Online ahead of print.

ABSTRACT

OBJECTIVES: Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS.

METHODS: We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure-free); serious adverse events (SAEs); discontinuations due to AEs.

RESULTS: We identified relevant data from two placebo-controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: -20% to 22%; p = 0.93] and 6% [-15% to 27%; p = 0.59], respectively), and both were statistically superior (p < 0.05) to licensed dose regimens of cannabidiol (10 or 20 mg/kg/day, with/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure-free intervals compared to fenfluramine (RD = 26% [CI: 8% to 44%; p < 0.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter.

SIGNIFICANCE: This NMA of RCT data indicates stiripentol, as a first-line add-on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add-on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision-making and the continued development of guidelines for the treatment of people with DS.

PLAIN LANGUAGE SUMMARY: This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS.

PMID:38427284 | DOI:10.1002/epi4.12923

Front Genet. 2024 Feb 15;15:1355962. doi: 10.3389/fgene.2024.1355962. eCollection 2024.

ABSTRACT

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin.

PMID:38425716 | PMC:PMC10902464 | DOI:10.3389/fgene.2024.1355962

Eur J Med Genet. 2024 Apr;68:104929. doi: 10.1016/j.ejmg.2024.104929. Epub 2024 Feb 28.

ABSTRACT

GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female child, who presented with some unique features such as sagittal craniosynostosis with scaphocephaly & bilateral choroid plexus cysts, alongside the core phenotype. We also report a novel frameshift variant in our patient & offer first evidence for the prenatal onset of some features.

PMID:38423276 | DOI:10.1016/j.ejmg.2024.104929

Sci Rep. 2024 Mar 1;14(1):5056. doi: 10.1038/s41598-024-55424-8.

ABSTRACT

Rare genetic diseases affect 5-8% of the population but are often undiagnosed or misdiagnosed. Electronic health records (EHR) contain large amounts of data, which provide opportunities for analysing and mining. Data mining, in the form of cluster analysis and visualisation, was performed on a database containing deidentified health records of 1.28 million patients across 3 major hospitals in Singapore, in a bid to improve the diagnostic process for patients who are living with an undiagnosed rare disease, specifically focusing on Fabry Disease and Familial Hypercholesterolaemia (FH). On a baseline of 4 patients, we identified 2 additional patients with potential diagnosis of Fabry disease, suggesting a potential 50% increase in diagnosis. Similarly, we identified > 12,000 individuals who fulfil the clinical and laboratory criteria for FH but had not been diagnosed previously. This proof-of-concept study showed that it is possible to perform mining on EHR data albeit with some challenges and limitations.

PMID:38424111 | PMC:PMC10904843 | DOI:10.1038/s41598-024-55424-8