531 results match your criteria: "Inherited Metabolic Disorders Overview"

: Cardiovascular disease is a leading cause of mortality globally and a major contributor to disability. Traditional risk factors, as initially established in the FRAMINGHAM study, have helped to stratify populations and identify patients for early intervention. Incorporating genetic factors enhances risk stratification tools, enabling the earlier identification of individuals at increased risk and facilitating more targeted and effective risk factor modifications.

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Effects of miRNAs in inborn error of metabolism and treatment strategies.

Postgrad Med J

January 2025

Department of Pediatric Metabolic Diseases, University of Health Sciences, Ankara Etlik City Hospital, Ankara 06170, Turkey.

Metabolism is the name given to all of the chemical reactions in the cell involving thousands of proteins, including enzymes, receptors, and transporters. Inborn errors of metabolism (IEM) are caused by defects in the production and breakdown of proteins, fats, and carbohydrates. Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules, ⁓19-25 nucleotides long, hairpin-shaped, produced from DNA.

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Biological Basis of Cell Trafficking: A General Overview.

J Inherit Metab Dis

January 2025

Department of Neurology and MetabERN; Esplugues de Llobregat, Synaptic Metabolism and Personalized Therapies Lab, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.

Cell trafficking is a tightly regulated biological process for the exchange of signals and metabolites between cell compartments, including four main processes: membrane trafficking (transport of membrane-bound vesicles), autophagy, transport along the cytoskeleton, and membrane contact sites. These processes are cross-sectional to cellular functions, ranging from the transportation of membrane proteins, membranes, and organelles to the elimination of damaged proteins and organelles. In consequence, cell trafficking is crucial for cell survival and homeostasis, serving as a cornerstone for cellular communication and facilitating interactions both with the surrounding environment and between different organelles.

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Inherited metabolic epilepsies-established diseases, new approaches.

Epilepsia Open

December 2024

Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Inherited metabolic epilepsies (IMEs) represent the inherited metabolic disorders (IMDs) in which epilepsy is a prevailing component, often determining other neurodevelopmental outcomes associated with the disorder. The different metabolic pathways affected by individual IMEs are the basis of their rarity and heterogeneity. These characteristics make it particularly challenging to establish their targeted therapies, and many of the IMEs are treated nowadays only symptomatically and supportively.

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Adeno-associated virus (AAV) vectors have demonstrated safety and efficacy for gene transfer to hepatocytes in preclinical models, in various clinical trials and from a clinical experience with a growing number of approved gene therapy products. Although the exact duration is unknown, the expression of therapeutic genes in hepatocytes remains stable for several years after a single administration of the vector at clinically relevant doses in adult patients with hemophilia and other inherited metabolic disorders. However, clinical applications, especially for diseases requiring high AAV vector doses by intravenous administrations, have raised several concerns.

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Dysmorphisms, or physical abnormalities in appearance, can vary in frequency and severity among individuals with inherited metabolic disorders (IMD). The prevalence of dysmorphisms in these disorders can range from rare occurrences to more common features, depending on the specific disorder and its genetic characteristics. It is important to note that not all individuals with IMDs will exhibit dysmorphic features, and the presence of such features may vary widely among different types of metabolic disorders.

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Article Synopsis
  • Kidney stone disease (KSD) is a growing global health issue, with around 30% of children and 1-5% of adults potentially having monogenic variants, yet genetic testing remains underutilized due to a lack of awareness and perceived benefits.
  • A study of 1675 patients showed that genetic testing yielded a positive result in about 20% overall, with a higher likelihood (26%) in pediatric patients compared to adults (8%), indicating the importance of age in diagnosis.
  • The most common genetic condition found was cystinuria, and the overall diagnostic yield decreased notably when excluding cases identifiable through other tests, highlighting the need for more awareness and application of genetic testing in KSD.
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Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent.

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Lysosomal storage diseases (LSDs) encompass a group of rare inherited metabolic disorders characterized by the accumulation of undegraded substrates within lysosomes, leading to multisystemic manifestations, including profound neurological involvement. This article provides a concise overview of the neurological manifestations of LSDs, with a focus on central nervous system (CNS) involvement and treatment strategies. While the paper intricacies of each LSD subtype and its associated CNS manifestations, it aims to provide a summary of the essential findings and implications.

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Newborn screening for SCID and severe T lymphocytopenia in Europe.

J Allergy Clin Immunol

November 2024

Laboratory for Paediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Article Synopsis
  • Newborn screening (NBS) programs in Europe started in the 1960s, expanding recently to include testing for severe combined immunodeficiency (SCID) through T-cell receptor excision circles (TRECs).
  • A survey sent to 46 European countries collected comprehensive data, with 38 countries responding, revealing that 17 have already implemented TREC-based NBS.
  • The findings indicate a need to reassess the definition of the target disease to include conditions beyond SCID and highlight the importance of international collaboration for improving universal TREC-based screening.
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Article Synopsis
  • Leigh syndrome (LS) is a severe mitochondrial disease caused by mutations in over 100 genes that impair cellular respiration and mainly affect brain function, leading to cognitive and motor issues.
  • Various model systems, including yeast, fruit flies, zebrafish, and mice, have been developed over 30 years to study the disease's mechanisms and symptoms.
  • Recent advancements in using induced pluripotent stem cells (iPSCs) enable researchers to examine LS mutations in human cells, facilitating high-throughput drug screening and the potential for personalized treatments.
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Metabolic impairments in neurodegeneration with brain iron accumulation.

Biochim Biophys Acta Bioenerg

January 2025

Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address:

Neurodegeneration with brain iron accumulation (NBIA) is a broad, heterogeneous group of rare inherited diseases (1-3 patients/1,000,000 people) characterized by progressive symptoms associated with excessive abnormal iron deposition in the brain. Approximately 15,000-20,000 individuals worldwide are estimated to be affected by NBIA. NBIA is usually associated with slowly progressive pyramidal and extrapyramidal symptoms, axonal motor neuropathy, optic nerve atrophy, cognitive impairment and neuropsychiatric disorders.

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Tofersen for SOD1 ALS.

Neurodegener Dis Manag

October 2024

Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

Article Synopsis
  • Amyotrophic lateral sclerosis (ALS) is a complex neurological disease that impacts muscle control, making research and clinical trials challenging due to its varied nature.
  • Genetic mutations causing ALS, particularly those involving SOD1, allow for targeted treatment strategies, such as the 'knock-down' approach that reduces harmful protein production.
  • Tofersen, an experimental treatment that decreases SOD1 mRNA, showed promising biomarker results, and although its Phase III trial didn’t hit its main goal, follow-up data indicate it may help slow down the progression of the disease in SOD1 ALS patients.
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White matter disorders with cerebral calcification in adulthood.

Handb Clin Neurol

September 2024

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom; Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom. Electronic address:

Article Synopsis
  • The chapter provides an in-depth look at adult-onset leukoencephalopathies associated with cerebral calcification (CC), focusing on diagnosis through age of onset, clinical features, and brain imaging methods.
  • It explains the differences between primary familial brain calcification (PFBC) and secondary forms, including various metabolic and genetic disorders, detailing specific genetic causes.
  • The diagnostic process involves family history, clinical assessments, and imaging techniques, with genetic testing being key for proper diagnosis and patient management involving a multidisciplinary approach.
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Neurological glycogen storage diseases and emerging therapeutics.

Neurotherapeutics

September 2024

Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA; Center for Advanced Spatial Biomolecule Research (CASBR), University of Florida, Gainesville, FL, USA. Electronic address:

Article Synopsis
  • * Patients with n-GSDs show varying neurological symptoms and require different treatment strategies compared to traditional GSDs, as recent studies have uncovered the genetic and biochemical mechanisms behind these conditions.
  • * New therapeutic approaches such as enzyme replacement therapy, substrate reduction therapy, and gene therapy have shown promising results in clinical trials, paving the way for improved treatment and better outcomes for n-GSD patients.
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Article Synopsis
  • * Management of dyslipidemia in pregnant women, especially those with inherited forms, requires tailored dietary adjustments and may involve pharmacological treatments, although these can be limited by cost and risks.
  • * A personalized, multidisciplinary approach is critical for optimizing health outcomes, with an emphasis on evidence-based practices and understanding the physiological changes in lipid metabolism during pregnancy.
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In recent years, mitochondria have gained significant interest in the field of biomedical research due to their impact on aging, human health, and other advanced findings in metabolic functions. The latest finding shows that metabolic interventions are a leading cause of several diseases, which has sparked interest in finding new therapeutic treatments. Apart from this, the unique inheritance of genetic material from mother to offspring can help scientists find ways to prevent mitochondrial inherited diseases.

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Acquired and Inherited Zinc Deficiency-Related Diseases in Children: A Case Series and a Narrative Review.

Pediatr Rep

July 2024

Pediatric Emergency Room and Emergency Medicine Unit, Emergency Department, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.

Article Synopsis
  • - Zinc deficiency is a critical health issue for children, leading to a variety of health problems and conditions that can be either acquired or inherited.
  • - This overview highlights the different symptoms, diagnostic difficulties, and treatment options for zinc deficiency in children, including issues like skin problems, slow growth, immune dysfunction, and neurological effects.
  • - Addressing zinc deficiency requires collaboration among healthcare professionals such as pediatricians, dermatologists, geneticists, and nutritionists to improve care and outcomes for affected children.
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Glycosaminoglycans in mucopolysaccharidoses and other disorders.

Adv Clin Chem

August 2024

Nemours Children's Health, Wilmington, DE, United States; University of Delaware, Newark, DE, United States; Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address:

Glycosaminoglycans (GAGs) are sulfated polysaccharides comprising repeating disaccharides, uronic acid (or galactose) and hexosamines, including chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. Hyaluronan is an exception in the GAG family because it is a non-sulfated polysaccharide. Lysosomal enzymes are crucial for the stepwise degradation of GAGs to provide a normal function of tissues and extracellular matrix (ECM).

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Article Synopsis
  • Thalassemia is a genetic blood disorder that affects many people globally, with around 50,000 to 60,000 infants diagnosed each year.
  • The primary treatment involves blood transfusions, which can lead to serious iron overload, managed through iron chelation therapy that may cause skin complications like rashes and photosensitivity.
  • The article outlines strategies to treat these skin issues, including patient education, regular skin checks, sun protection, topical treatments, and the need for collaboration between hematologists and dermatologists for better patient care.
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Article Synopsis
  • The report examines clinical, genetic, and biochemical characteristics of individuals with a confirmed congenital disorder of glycosylation (CDG) participating in the FCDGC Natural History cohort after five years of study.
  • A total of 333 subjects were enrolled, with 280 having available genetic data; this included a nearly even split between males and females, with ages ranging from infancy to 71 years.
  • The study found developmental delays to be the most common symptom leading to diagnosis, occurring in 77% of participants, with an average delay of 2.7 years from symptom onset to diagnosis, and nearly all individuals displaying some developmental differences at the time of enrollment.
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Inborn errors of the malate aspartate shuttle - Update on patients and cellular models.

Mol Genet Metab

August 2024

Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address:

The malate aspartate shuttle (MAS) plays a pivotal role in transporting cytosolic reducing equivalents - electrons - into the mitochondria for energy conversion at the electron transport chain (ETC) and in the process of oxidative phosphorylation. The MAS consists of two pairs of cytosolic and mitochondrial isoenzymes (malate dehydrogenases 1 and 2; and glutamate oxaloacetate transaminases 1 and 2) and two transporters (malate-2-oxoglutarate carrier and aspartate glutamate carrier (AGC), the latter of which has two tissue-dependent isoforms AGC1 and AGC2). While the inner mitochondrial membrane is impermeable to NADH, the MAS forms one of the main routes for mitochondrial electron uptake by promoting uptake of malate.

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The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this manuscript was to provide a comprehensive overview on liver involvement in LSDs, focusing on clinical manifestation and its pathomechanisms. Gaucher disease, acid sphingomyelinase deficiency, and lysosomal acid lipase deficiency were thoroughly reviewed, with hepatic manifestation being a dominant clinical phenotype.

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Background: The outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims to give a comprehensive overview of clinical and molecular characteristics of pediatric FA MB patients.

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Article Synopsis
  • The term non-alcoholic fatty liver disease (NAFLD) has faced criticism for its use in both children and adults, leading to the introduction of metabolic (dysfunction)-associated fatty liver disease (MAFLD), which better reflects the condition's complexities.
  • The rise of MAFLD parallels increasing obesity rates and positions it as a leading cause of chronic liver disease, especially among children, while recognizing the potential for additional metabolic disorders.
  • Despite progress in understanding MAFLD's multifactorial causes, limitations in non-invasive diagnostic methods remain, with dietary and lifestyle changes being key to management, supplemented by ongoing exploration of new treatments.
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