Materiały źródłowe

• #1 Inherited metabolic disorders // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/inherited-metabolic-disorders

  Treatment depends on the type of inherited metabolic disorder and how severe it is. Because there are so many types of inherited metabolic disorders, treatment can vary a great deal. A few examples of treatments include special diets, enzyme replacement, vitamin therapy, medicines and liver transplants. Sometimes care begins with a stay in the hospital. For some types of inherited metabolic disorders, there are no treatments currently available. […] Life-long care with regular healthcare visits is important to take care of problems early and adjust treatment as needed.

• #1 Inborn Errors of Metabolism Treatment & Management: Approach Considerations, Medical Care, Diet

  https://emedicine.medscape.com/article/804757-treatment

  Goals of treatment for patients with an IEM are prevention of further accumulation of harmful substances, correction of metabolic abnormalities, and elimination of toxic metabolites. […] With appropriate therapy, patients may completely recover without sequelae. […] Treatment of patients with a known IEM should be disease and patient specific. […] Strict adherence to dietary and pharmacologic regimen is recommended for patients diagnosed with an IEM. […] Medical therapy specific for the IEM diagnosed will need to be continued, usually for life. […] Once toxic metabolites have been normalized, protein can be reintroduced using an essential amino acid solution, initially at 0.5-0.75 g/kg/day and gradually increased; for amino and organic acid disorders and urea cycle defects, protein intake should be restricted to 40-50% of recommended daily allowance (RDA);

• #1 Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01727-2

  The Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disability (collectively treatable IDs). […] The most frequent therapeutic interventions were nutritional, pharmacological and vitamin and trace element supplementation. […] Although there has been much attention to gene-based and enzyme replacement therapy, the majority of effective treatments are nutritional, which are relatively affordable, widely available and (often) surprisingly effective. […] The ideal outcome of therapy for a treatable ID is the improvement of IQ and related developmental scores. […] Effect(s) of treatment outcomes were defined as shown in Table 1A. We included treatments if they had a direct effect on ID (improvement or stabilization), or if there was a reasonable expectation that ID would be improved by significant improvement of other symptoms such as seizures or severe movement disorders thus making development possible.

• #1 Inherited Metabolic Disorders: Types, Signs, Causes & Treatment

  https://www.webmd.com/a-to-z-guides/inherited-metabolic-disorder-types-and-treatments

  Limited treatments are available for inherited metabolic disorders. The essential genetic defect causing the condition cant be corrected with the technology we have right now. Instead, treatments try to work around the problem with metabolism. […] There are presently therapies used for some of the inherited metabolic disorders that are quite efficacious, including medications and dietary therapy, and can help to varying degrees of effect depending on the particular disorder, Tramontana says. […] But, he continues, many of these disorders have no treatment, and for those that do, such treatments may not have much evidence to support their use. […] Treatments for genetic metabolic disorders follow a few general principles: Reduce or eliminate intake of any food or drug that cant be metabolized properly. Replace the enzyme or other chemical that is missing or inactive to restore metabolism to as close to normal as possible. Remove toxic products of metabolism that build up due to the metabolic disorder.

• #1 Inherited Metabolic Diseases Program | ontario.ca

  http://www.ontario.ca/page/inherited-metabolic-diseases-program

  The Inherited Metabolic Diseases (IMD) Program, through the Ministry of Health, covers the full cost of certain outpatient drugs, supplements and specialty foods used in the treatment of specific inherited metabolic disorders. […] The Inherited Metabolic Diseases Program will cover the full cost of some treatments, such as: drugs (for example, L-carnitine), supplements (for example, vitamins, antioxidants), low-protein foods (for example, pasta, buns), modified L-amino acid mixtures or medical foods (for example, essential amino acid mix), infant formula (for example, Nutramigen A+), nutritional products (for example, Boost, Ensure) used in enteral, or tube feeding. […] To ensure that appropriate treatments are being provided to IMD Program patients, special treatment facilities have been designated to distribute the funded products.

• #1 Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01727-2

  Our data show that although there has been much attention given to gene-based and enzyme replacement therapy, the majority of currently available, effective treatment strategies are nutritional, via dietary interventions and supplementation of vitamins and trace elements. […] For some IMDs, timely and continued treatment ensures patients live (almost) normal lives, with Phenylketonuria (PKU) being the most prominent example. […] The results emphasize the importance of testing for treatable IEMs in all patients with unexplained ID, as earlier diagnosis provides the opportunity to mitigate or possibly prevent irreversible brain damage.

• #1 Metabolic Disorders | IU Health

  https://iuhealth.org/find-medical-services/metabolic-disorders

  Physicians at IU Health lead the state in newborn screening of metabolic disorders and treatment for both adults and children. […] Metabolic disorders are lifelong diseases, but early treatment can often alter their natural progression. You inherit most metabolic disorders. […] Most treatable metabolic conditions require special diets to ensure proper health and prevent complications. […] To protect the body’s systems, you must follow a special restricted-protein diet. […] At the PKU treatment center, the only one of its kind in the state, physicians, dietitians, social workers and counselors work closely with you and your family to assist you in managing this complicated and costly disease. […] Babies, children and adults with galactosemia must avoid milk and all dairy products from milk in their diets. Dietary restrictions should begin as soon as possible.

• #1 Metabolic Clinic | Children’s Hospital Colorado

  https://www.childrenscolorado.org/doctors-and-departments/departments/genetics/metabolic/

  The metabolic nutritionists develop individualized plans of dietary treatment for each patient who has a confirmed diagnosis that is managed by diet. This includes disorders of amino acids, organic acids, and carbohydrate metabolism. […] The IMD Clinic provides genetic counseling and education related to inborn errors of metabolism. This may include an explanation of the patient’s diagnosis, mode of inheritance, risk of recurrence in future children or grandchildren, and information regarding prenatal diagnosis if applicable. […] The Lysosomal Disorders Program is a comprehensive program providing diagnosis, management, treatment, education, and genetic counseling for these disorders. Currently, the program is involved in the coordination of clinical enzyme replacement therapy, recruitment and entry into disease registries, and participation in clinical research trials.

• #1 Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01727-2

  The different types of treatment as defined in Table 1A are shown per disorder in Table 3. Nutritional therapy was the most frequently used treatment strategy (32%), followed by pharmacological therapy 22%, vitamin and trace element substitution 22%, solid organ transplantation 8%, hematopoietic stem cell transplant 4%, enzyme replacement therapy 3%, gene-based therapy 2% and other therapy 7% (multiple treatments per disease entity were possible). […] Treatment prevented, halted, or slowed clinical deterioration in 62%, improved neurological manifestations (incl. neuro-imaging) in 47%, systemic manifestations in 44% and psychomotor/cognitive development/IQ in 37%; it prevented acute metabolic decompensation in 30%, improved seizure/epilepsy control in 22% and improved behavioural/psychiatric disturbance(s) in 21%.

• #1 Inborn Errors of Metabolism Treatment & Management: Approach Considerations, Medical Care, Diet

  https://emedicine.medscape.com/article/804757-treatment

  Pharmacologic therapy to increase activity of abnormal cofactor-dependent enzymes (eg, thiamine [B-1] 5-20 mg/day PO up to 500 mg/day, biotin 5-20 mg/day PO, riboflavin [B-2] 200-300 mg PO tid, cobalamin [B-12] 1-2 mg/day IM) may be given; vitamins may be given empirically. […] Transplantation (organ or bone marrow) […] Enzyme replacement therapy […] Gene therapy.

• #1 Inborn Errors of Metabolism (IEM) – Inherited Metabolic Disorders

  https://my.clevelandclinic.org/health/diseases/17962-inherited-metabolic-disorders

  Inborn errors of metabolism are a group of genetic conditions that affect the function of your metabolism. Treatment includes changes to your diet or taking medicines to help your body process certain foods. […] Treatment for inborn errors of metabolism varies based on the type but could include: Changing your diet: Since your body has trouble processing foods and beverages, removing certain food items from your diet can prevent flares of symptoms. Taking medicine: Your provider might recommend taking certain medicines that can help your metabolism function as expected. Drugs could include enzyme or chemical replacements. Undergoing dialysis: A procedure that removes toxins out of your blood. Organ transplant: To treat severe cases of IEM, a liver transplant might be necessary. […] Your provider might recommend taking certain medicines to treat inborn errors of metabolism (IEM). The medicine will vary based on the type of IEM and could include: Glucose solution. Insulin. Sodium benzoate or sodium phenylacetate. Amino acid supplements. Enzyme replacement. Dietary supplements. […] Most conditions are easily treatable with medication and dietary changes. Early detection and treatment lead to the best prognosis.

• #1 Inherited metabolic disorders associated with hypoglycaemia in adulthood: a narrative review – Dawson – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6373/html

  Inherited metabolic disorders (IMD) are conditions caused by mutations in a gene encoding an enzyme, transporter protein or enzyme cofactor involved in generating energy or removing waste products of metabolism. […] In the last two decades, better lifelong holistic care and advances in gene sequencing technology have improved our understanding of how IMDs affect adults. Consequently, attenuated IMD phenotypes are increasingly being recognised. […] Acute management of fatty acid oxidation disorders requires administration of high dose glucose orally as a glucose polymer if tolerated, otherwise intravenously as a 10% glucose solution, aiming to maintain a blood glucose level greater than 5.5 mmol/L. […] The aim of treatment is to maintain normoglycaemia by avoidance of fasting. Children and some adults require overnight feeding with glucose polymer administered via a nasogastric or gastrostomy tube.

• #1 Inherited metabolic disorders associated with hypoglycaemia in adulthood: a narrative review – Dawson – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6373/html

  Hypoglycaemia responds well to diazoxide. […] Hypoglycaemia is a common presenting problem at all ages. However, in adults, it is significantly more likely to be of an endocrine rather than genetic aetiology. […] The increased availability of confirmatory genetic testing in recent years has enhanced our understanding of the relative pathogenicity of specific mutations, a consequence of which is the recognition of attenuated phenotypes of disorders historically considered to be paediatric conditions.

• #1 Metabolic Disorders: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders/treatment

  Treating metabolic disorders primarily involves lifestyle changes, including diet, physical activity, and medication. […] A dietitian can help you find a diet and exercise plan that works for you. […] If healthy lifestyle changes don’t work, you may consider medication. Sometimes, your doctor may recommend a drug treatment option called Metformin, especially if labs show high blood glucose levels or obesity that don’t respond to dietary and lifestyle changes. […] Our health care professionals are skilled at treating metabolic disorders. Without treatment, symptoms will worsen and lead to significant complications.

• #1 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  Treatment for Wilson’s disease is effective if diagnosis occurs before the onset of life-threatening symptoms. The goal of treatment is to remove excessive copper from the body and prevent it from re-accumulating. […] Medical therapy, therefore, should be instituted at the time of diagnosis, and family members should be screened for subclinical disease. […] Treatment of CTX with CDCA, a bile acid, will arrest, but generally will not reverse the frequently devastating neurological deterioration seen in these patients. […] Traditional therapies for IMDs include dietary therapy, such as protein restriction, cofactor supplements, and so on. Evolving therapies include organ transplantation and enzyme replacement. […] A combined approach and management by an ophthalmologist, paediatrician, biochemist, and medical geneticist is warranted in most cases. […] Recent advances in diagnosis and treatment have significantly improved the prognosis for many infants with inborn errors of metabolism.

• #1 Inherited Metabolic Disease | Division of Medical Genetics | Stanford Medicine

  https://med.stanford.edu/medicalgenetics/Metabolicdisease.html

  There are different treatments tailored to the specific inherited metabolic disease. A common treatment is diet modification. Other possible treatments include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and organ transplantation. […] Enzyme replacement therapy (ERT) is a treatment that replaces missing enzymes in individuals with lysosomal enzyme deficiencies. The treatment most often involves weekly or biweekly intravenous (IV) infusions depending on the enzyme. Some are administered directly into the central nervous system (intrathecal). ERT is not curative but can ameliorate symptoms or slow the progression of the disease. […] Hematopoietic stem cell transplantation (HSCT) can be performed for a small number of inborn errors of metabolism to prevent or slow-down the development of symptoms. Outcomes tend to depend on the clinical stage of the disease and in some instances, it can be recommended before symptoms start. […] The Program for Inherited Metabolic Disorders (PIMD) was established to promote the development of stem cell and gene therapies for metabolic diseases. The goal is to develop one-time therapies that are more effective and safer than currently available ones.

• #1 Advances in the Treatment of Inherited Metabolic Diseases | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4615-8303-5_5

  Major advances have been made in the elucidation of the molecular pathologies of inherited metabolic diseases during the past two decades. […] However, in spite of these major diagnostic achievements, patients and their families have become increasingly disappointed by the absence of specific therapies for most of these debilitating disorders. […] Enzyme therapy IV: A method for determining the in vivo fate of bovine -glucuronidase in -glucuronidase deficient mice. […] Enzyme therapy: Differential in vivo retention of bovine hepatic, renal and splenic -glucuronidases and evidence for enzyme stabilization by intermolecular exchange. […] Enzyme replacement therapy in Gaucher disease: Preliminary clinical trial of a new enzyme preparation. […] Status of enzyme replacement therapy for Gaucher disease. […] Enzyme replacement in Pompe disease with an -glucosidase low density lipoprotein complex. […] Enzyme therapy in Fabry disease: Differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic -galactosidase.

• #1 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  The diagnosis of inborn errors of metabolism is challenging for most physicians. […] Recent advances in the diagnosis and treatment of IMDs have substantially improved the prognosis for many of these conditions. […] Early diagnosis is crucial for three reasons. First, IMDs are rapidly progressive and cause irreversible damage early in the course of the disease. Second, the treatment can often be effective, if commenced early and long-term outcome may be improved. Lastly, correct early diagnosis helps in genetic counselling. […] The latest breakthroughs in the diagnosis and treatment of IMDs have significantly improved the prognosis for many of these conditions. […] Enzyme-replacement therapy (ERT) should be given early to patients with Fabry’s disease if resources allow before irreversible pathology sets in.

• #1 Inherited Metabolic Myopathies: Current Diagnosis and Treatment Approaches – Medical Journal of Bakirkoy

  https://www.bakirkoymedj.org/articles/inherited-metabolic-myopathies-current-diagnosis-and-treatment-approaches/doi/BMJ.galenos.2021.57804

  This review aims to make the differential diagnosis of metabolic myopathies from other structural myopathies and present current diagnosis and treatment approaches. […] Hence, it requires specific laboratory diagnostic methods and has specific treatments. […] Enzyme replacement therapy (ERT), which is a recombinant human GAA (rhGAA), has given a reasonable positive response. […] In addition to ERT, positive, supportive effects of diet (high protein and branched-chain amino acids diets have been used as alternative energetic substrates) and benefits of the antioxidant treatments have also been reported. […] A recommended activity management targets to increase both capacity and muscle strength with the moderate-intensity exercise of 150 minutes per week distributed over 5 days per week to increase heart rate by 60%-70%.

• #1 Pediatric metabolic diseases – Children’s Health Metabolic Clinic

  https://www.childrens.com/specialties-services/conditions/metabolic-disease

  The clinic provides diagnostic evaluations of children, from birth to 18 years old, in whom a metabolic disorder is considered. Therapeutic management is provided for children with diagnosed inborn errors of metabolism, ages birth to 21 years. We work closely with parents and families to provide treatment and support to improve clinical outcomes. […] We coordinate clinically available enzyme replacement therapy for these conditions. Childrens Health Special Procedures Clinic nurses provide weekly or biweekly enzyme replacement with oversight of the metabolic physicians. […] Dietary management – An individualized plan of dietary treatment is developed for each patient who has a confirmed diagnosis that is managed by diet. This includes disorders of amino acids, organic acids, and carbohydrate metabolism.

• #1 Inherited Metabolic Disorders Program | Children’s National Hospital

  https://www.childrensnational.org/get-care/departments/inherited-metabolic-disorders-program

  The Inherited Metabolic Disorders Program of the Childrens National Rare Disease Institute has partnered with the MedStar Georgetown Transplant Institute to establish a Metabolic Transplant Program. There are currently no cures for inherited metabolic disorders, and many of these conditions are associated with frequent hospitalizations and long-term intellectual disability. […] Liver transplantation may effectively treat some of these conditions, stabilizing intellectual outcomes and preventing other disease manifestations. […] The onsite lab allows for faster turnaround of laboratory and genetic testing for our patients.

• #1 Inherited metabolic disorders associated with hypoglycaemia in adulthood: a narrative review – Dawson – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6373/html

  Its use has transformed the outlook for people with GSD, especially GSD I, by aiding growth and development in children, progression of puberty in adolescents and protecting against an acute metabolic crisis precipitated by fasting or illness at any age. […] Long-term, adults almost universally develop hepatic adenomas but these are particularly prevalent and develop at an earlier age if metabolic control has been poor. […] Liver transplantation fully corrects the genetic defect and is potentially curative for both hypoglycaemia and long-term hepatic complications. […] The key to the diagnosis is recognition of the association of symptoms with ingestion of fructose-containing foods and a positive effect from withdrawal of these foods from the diet. […] The hepatic and renal tubular complications of the condition are reversible by complete withdrawal of fructose from the diet.

• #1 Inherited Metabolic Disorders | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/pediatrics/cancer-care/types/pediatric-blood-disorders/about-pediatric-blood-disorders/inherited-metabolic-disorders

  Inborn errors of metabolism are a diverse group of disorders caused by an inherited deficiency or defect in a single enzyme or protein. […] At MSK Kids, we understand how devastating it is to hear your child has one of these serious disorders, and we know you want to do everything you can to give your child the best life possible. […] The only effective treatment for cALD is a stem cell transplant before the disease becomes too advanced. […] Treatment is possible for juvenile and adult MLD. A stem cell transplant is the only known cure and should be done before the disease becomes too advanced. […] Treatment with a stem cell transplant early in life is the only way to stop the disease from progressing. […] The MSK Kids team works together to diagnose these disorders and start treatment as early as possible. Children with these inborn errors of metabolism have access to our expertise in stem cell transplantation, the only effective therapy.

• #1 Gene therapy for inherited metabolic diseases

  https://sciendo.com/article/10.34763/jmotherandchild.20202402si.2004.000009

  Over the last two decades, gene therapy has been successfully translated to many rare diseases. […] Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a disease-changing therapeutic option for these patients. […] We discuss the respective advantages and pitfalls of these gene therapy strategies and review their application in IMD, providing examples of clinical trials with lentiviral or adeno-associated viral gene therapy vectors in rare diseases. […] The rapid development of the field and implementation of gene therapy as a realistic therapeutic option for various IMD in a short term also require a good knowledge and understanding of these technologies from physicians to counsel the patients at best.

• #1 Gene Therapy for Inherited Metabolic Diseases

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8518100/

  The strategies and delivery technologies developed to improve the efficacy and the safety of gene therapy are a field of intense research and interest. […] Gene therapy is the transfer or editing of a genetic material to cure a disease. […] In vivo gene therapy refers to the injection of a vector encoding the gene of interest or molecular tools for gene editing, directly into a tissue or into the systemic circulation to generate therapeutic outcomes in specific or multiple organs. […] Ex vivo gene therapy involves manipulation of a target cell population outside of the body, often as part of autologous stem cell therapies, in which a patients own cells are genetically modified with gene editing or gene supplementation and then engrafted back into the patient. […] The gene therapy field was recently revolutionised by the introduction of genome editing tools, which includes nucleases engineered to modify the genome at precise loci.

• #1 Gene Therapy for Inherited Metabolic Diseases

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8518100/

  Over the last two decades, gene therapy has been successfully translated to many rare diseases. […] Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a disease-changing therapeutic option for these patients. […] In the past 20 years, gene therapy has emerged as a disease-changing treatment for these disorders. […] Gene therapy had driven fantastic hope in the mid-1990s when addressing severe combined immunodeficiency (SCID) due to deficiency of the enzyme adenosine deaminase (ADA-SCID). […] Subsequently, the research focused on safer delivery vectors and successful results have currently been reported for various inherited rare diseases such as Lebers congenital amaurosis, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, haemophilia B and many other IMDs, leading to first market authorisations in Europe and in the USA in 2012 and 2017, respectively.

• #1 Inherited Metabolic Diseases from Past to Present: A Bibliometric Analysis (1968–2023)

  https://www.mdpi.com/2227-9067/10/7/1205

  Early diagnosis can reduce mortality and morbidity by providing early treatment for inherited metabolic diseases. For this reason, screening for the highest number of inherited metabolic diseases in newborns is essential, considering treatment efficacy, ethical issues, and cost-benefit balance. We believe that newborn screening will maintain its popularity in the future. […] In addition to enzymatic treatments, clinical studies have been carried out in gene therapy in recent years. […] The most recent treatment approach for metabolic diseases is correcting the primary genetic defect. In this approach, conventional gene therapy is applied by delivering a vector containing the correct coding DNA (cDNA) sequence of the defective gene to the host rather than resolving the endogenous genetic defect. Gene therapy has been successfully applied in preclinical trials of inherited metabolic diseases such as glycogen storage type 1a, familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hereditary tyrosinemia type 1.

• #1 Gene Therapy for Inherited Metabolic Disorders Program | Children’s Hospital of Philadelphia

  https://www.chop.edu/centers-programs/genetherapy4inheritedmetabolicdisorders

  The Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program at Childrens Hospital of Philadelphia (CHOP) was created by a trailblazing group of researchers and clinicians dedicated to treating inborn errors of metabolism. […] There are currently no cures for IEMs only therapies to help manage them. […] Our researchers are studying how we can better treat or even cure diseases by targeting specific genes. CHOP is a leader in developing and administering two types of gene therapy. […] Researchers at Childrens Hospital of Philadelphia and the University of Pennsylvania are developing a platform to help fast-track personalized gene-editing therapies for patients with urea cycle disorders and other rare metabolic diseases.

• #1 New mRNA therapy shows promise in treating 'ultrarare’ inherited disease | Live Science

  https://www.livescience.com/health/medicine-drugs/new-mrna-therapy-shows-promise-in-treating-ultrarare-inherited-disease

  Initial trial results suggest that a new mRNA therapy may be able to safely and effectively treat propionic acidemia, a rare metabolic disorder. […] There is currently no cure for PA. Instead, treatments aim to manage the symptoms of the disease, by getting patients to follow a carefully controlled, low-protein diet, for example, and frequently replacing lost fluids to prevent dehydration. Patients may also require liver transplants, as replacing this key organ involved in metabolism can help somewhat restore their levels of functioning PCC. […] The new treatment, called mRNA-3927, contains mRNA needed to make the two subunits of PCC that are faulty in patients with PA, thus helping to replenish stocks of working enzymes in the body. […] Eight of the 16 participants had experienced MDEs in the year before the trial, and these patients saw an overall 70% drop in their rate of MDEs during treatment.

• #1 New mRNA therapy shows promise in treating 'ultrarare’ inherited disease | Live Science

  https://www.livescience.com/health/medicine-drugs/new-mrna-therapy-shows-promise-in-treating-ultrarare-inherited-disease

  „This research could potentially improve outcomes for patients with propionic acidemia, who are at risk for recurrent illnesses requiring hospitalization, impaired growth and development, and early mortality,” Dr. Dwight Koeberl, a professor of pediatrics at Duke University School of Medicine in North Carolina who was not involved in the research, told Live Science in an email. […] After determining the optimum dose of mRNA-3927, the team hopes to assess the treatment’s longer term safety and effectiveness over the course of a year, to see if these promising findings endure.

• #1 Insurance coverage of medical foods for treatment of inherited metabolic disorders | Genetics in Medicine

  https://www.nature.com/articles/gim201346

  Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. […] Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources. […] The use of medical foods, modified low-protein foods, amino acid supplements, and high doses of vitamins for individuals with IMDs is not merely an optional, alternative food choice but rather a medical necessity. […] The prepared formulas that comprise the major part of the medical foods used for IMD treatment are more expensive than standard infant formulas. […] Overall, the parents surveyed indicated that 80% of children used at least two of the surveyed product types and 48% used three or more. […] Although 99% percent of the children in our survey had some type of health-care coverage, the insurance often did not provide complete coverage for medical foods, modified low-protein foods, supplements, or feeding supplies necessary for management of an IMD.

• #1 Diagnosis and Treatment of Inherited Metabolic Disorders – Pediatric Neurology and Neurosurgery | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/inherited-metabolic-disorders/diagnosis-and-treatment

  Your child’s healthcare team includes pediatric neurologists, genetics experts, registered dietitians, nurses, child life specialists, social workers, and any other professionals needed to provide care, all in one location. […] At the Children’s Hospital of New York, the pediatric neurology team takes a multidisciplinary approach that focuses on the whole child and offers them the best opportunity to enjoy a normal transition from childhood to adulthood. […] Children who have a lifelong need for specialized care, such as those with inherited metabolic disorders, are embraced by our care teams. […] If your child has a diagnosis of a metabolic disorder, our multidisciplinary team of specialists provide treatment specific to each patient’s metabolic condition. […] This may include dietary management with a metabolic nutritionist, enzyme replacement therapy and, in advanced cases, transplantation for bone marrow, liver, kidney or heart. […] Genetic counseling may be recommended to provide information on the recurrences of the metabolic disorder and any available testing.

• #1 Inherited Metabolic Disorders Care at OHSU

  https://www.ohsu.edu/doernbecher/inherited-metabolic-disorders

  OHSU Doernbecher Childrens Hospital provides state-of-the art care for people with inherited metabolic disorders. We offer: […] Inherited metabolic disorders often cant be cured. In most cases, people have them for life. We focus on getting metabolism as close to normal as possible. […] Our team meets weekly to discuss patients cases and coordinate treatment plans. Each patient may see a doctor, nurse practitioner, nurse, dietitian and genetic counselor. We regularly check each patients growth, nutrition and development. […] Treatment can include: […] Enzyme replacement or other supplements to help with metabolism […] Medications that help the body get rid of certain substances. […] The OHSU Metabolic Food Room provides medical foods and formulas for patients with inherited metabolic disorders.

• #1 Metabolic Disorders

  https://www.physio.co.uk/what-we-treat/learning-difficulties/metabolic-disorders.php

  Treatment for metabolic disorders begins by addressing the imbalance in chemicals in the body due to the disorder. Treatment options for your child include medication, vitamin and mineral supplements, counselling, dietary advice, surgery and physiotherapy. […] It is essential that your child with a metabolic disorder receives holistic therapy from a multi-disciplinary team of specialists. […] Your child will be assessed by a specialist physiotherapist carrying out a variety of functional activities such as crawling, sitting, standing, walking, running and climbing stairs depending on their age and level of mobility. […] An exercise plan will be provided for you to carry out at home on a regular basis with your child. […] The exercises and treatment sessions will be fun but challenging in order to motivate your child and encourage participation and progress.

• #1 Five questions about metabolic disorders – Metabolic disorders at the heart of Radio 3FM Serious Request – Radboudumc

  https://www.radboudumc.nl/en/news-items/2024/five-questions-about-metabolic-disorders

  From December 18 to 24, Radio 3FM Serious Request will take action for Metakids, a foundation supporting children with metabolic disorders, where the bodys metabolism doesn’t function properly. At Radboudumc Metabolic Disorders Expertise Center, we treat many children and adults with metabolic disorders. […] Metabolic disorders cannot be cured, but treatments are available for some patients that reduce symptoms or extend life, such as medical diets or medications. Lefeber explains: Our body needs various substances to function. If one substance is missing, it can sometimes be added through a diet. Or, if a substance isnt broken down properly, it can be removed from the diet. […] For 85% of metabolic disorders, no medication exists yet. However, care focuses on improving the quality of life. Patients with mitochondrial disorders or glycosylation disorders undergo thorough investigations at Radboudumc, including brain scans, muscle and heart ultrasounds, and consultations with physiotherapists, speech therapists, psychologists, and others. Van der Meijden adds: This approach ensures that patients leave with a treatment plan and follow-up care, especially for those who live far away.

• #1 Metabolic Disorders – Children’s Hospital of Orange County

  https://choc.org/programs-services/metabolic-disorders/

  Our specially trained team of experts provides comprehensive services including: Diagnostic evaluation, Nutritional assessment, Genetic counseling, Long-term management for individuals with inborn metabolic disorders. […] CHOC specialists work together as a team to discuss your child’s case and determine the best course of treatment. […] Our team also collaborates with specialized dietitians, social workers, respiratory therapists, nurses and nurse practitioners, rehabilitation therapists, pharmacists, speech and occupational therapists and child life specialists to develop a unique treatment plan for your child. […] We specialize in the diagnosis and treatment of inborn errors of metabolism, including organic acidemias, urea cycle defects, fatty acid oxidation defects, glycogen storage disorders, lysosomal storage disorders and mitochondrial diseases among others.

• #1 Dietary Treatment For Metabolic Disease

  https://www.medschool.lsuhsc.edu/genetics/louisiana_genetics_and_hereditary_health_care_dietary_treatment.aspx

  Diet is the primary – and often the only – treatment. […] The principles are the same. Food providing the substance that accumulates at the blocked pathway is restricted so that harmful amounts won’t build up. […] Dietary treatment of PKU begins with limiting the amount of phenylalanine going into the blocked pathway. […] A special metabolic formula must also be included in the diet. […] Good dietary treatment of PKU means maintaining that perfect balance of phenylalanine, protein, and calories that supports normal growth and health, but doesn’t cause harm. […] The success of treatment can be monitored by regularly measuring phenylalanine levels in the blood. […] Compliance with the restrictions of metabolic diets is often a struggle. […] Dietary treatment is successful for many metabolic diseases that could not be treated even 10 years ago, and can make it possible for people with metabolic disease to live normal, healthy lives. […] For now, diet is the medical treatment, and should be followed with care throughout life.

• #1 Causes, Symptoms & Stem Cell Treatment for Metabolic Diseases

  https://stemcellthailand.org/therapies/metabolic-diseases/

  Regular follow-up with healthcare providers is crucial for all metabolic diseases to monitor treatment response and disease progression. […] Stem cell therapy represents a promising approach to treating metabolic disorders, offering the potential for long-term solutions and improved patient outcomes. […] While more research is needed to fully understand this treatments safety and efficacy, early human clinical trial results are encouraging. […] The cellular treatment for metabolic conditions will require a minimum of 10-12 days in Bangkok.

• #1 Insurance coverage of medical foods for treatment of inherited metabolic disorders | Genetics in Medicine

  https://www.nature.com/articles/gim201346

  Our observations show that families had significant OOP expenses for treatments that are essential for these complex disorders. […] We found that insurance or other resources do not consistently cover costs of medical foods used to treat IMDs, potentially resulting in inequities in access to these essential products.

• #1 Gene Therapy for Inherited Metabolic Diseases

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8518100/

  Various strategies to efficiently deliver nucleic acids to target organs have been developed over the last 30 years and are summarised with their respective advantages and pitfalls. […] In recent years, ex-vivo gene therapy trials involving SIN-lentiviral correction of HSC have shown strong clinical data in treating a range of severe monogenic childhood diseases, including X-SCID. […] This programme illustrates the major clinical benefits of this gene therapy approach for neurodegenerative diseases. […] The standard of care relies on injections of recombinant FIX, an expensive therapy for public healthcare systems with an annual cost of US$300,000. […] This haemophilia B programme has received breakthrough therapy designation by the FDA. […] Gene therapies have revolutionised the last half century from science fiction to the first commercialised products. […] This novel therapy option will find its place among other available therapies, alone or in combination if necessary.

• #1 Gene Therapy for Inherited Metabolic Diseases

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8518100/

  A massive obstacle to the translation of gene therapy is the high prevalence of immune response against the vectors, either pre-existing when the patient has been previously exposed to the wild-type viral serotype used as gene therapy vector, or after exposure to the vector in the case of a re-injection is required. […] In most IMDs, an early treatment is essential to prevent debilitating complications, long-term sequelae and potentially death. […] Earlier, time for development of a promising gene therapy product from the first patient injected in a clinical trial to market authorisation has been slow from 8 to 16 years, although it is expected that the next products to be authorised might be developed at a quicker pace at present that the process has been successfully optimised with the first pioneering products.

• #1 The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11707409/

  Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. […] A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment. This study aimed to identify all treatable IEMs through a scoping literature review, followed by data extraction and analysis according to the Treatabolome principles. […] The most common treatment strategies were pharmacological therapy (34%), nutritional therapy (34%), and vitamin and trace element supplementation (12%). […] Presently, drug repurposing is gaining increasing importance. […] Gene therapies (e.g., hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy) and RNA therapies (e.g., volanesorsen in lipoprotein lipase deficiency) are emerging as promising therapeutic interventions for patients with IEMs.

• #1 Inherited Metabolic Disorders: Types, Signs, Causes & Treatment

  https://www.webmd.com/a-to-z-guides/inherited-metabolic-disorder-types-and-treatments

  Treatment may include such measures as: Following special diets that cut out certain nutrients. Taking enzyme replacements or other supplements that support metabolism. Treating the blood with chemicals to detoxify dangerous metabolic by-products. […] Whenever possible, a person with an inherited metabolic disorder should get care at a medical center experienced with these rare conditions. […] Experts continue to search for effective ways to treat these disorders. […] There are new and promising therapies coming out in the realm of gene therapy, enzyme replacement therapy, and prenatal therapies in fetuses with a known diagnosis, Tise says.

• #1 Inherited Metabolic Diseases from Past to Present: A Bibliometric Analysis (1968–2023)

  https://www.mdpi.com/2227-9067/10/7/1205

  Inherited metabolic diseases are rare diseases caused by a genetic mutation and have unique biochemical, clinical, and pathophysiological consequences depending on the specific biochemical pathway affected. Clinicians have become more knowledgeable in recent years about the pathophysiology, early diagnosis, and treatment of inherited metabolic diseases because of advances in genetics and biochemistry. Early diagnosis and treatment’s positive contribution by the recently increasing number of studies gives rise to survival, reduces morbidity in inherited metabolic diseases, and causes the introduction and increase of prenatal diagnosis methods and postnatal screening programs to diagnose these diseases. […] Newborn screening was the main topic that clinicians researching inherited metabolic diseases were most interested in. Newborn screening, first initiated in the 1960s to diagnose patients with phenylketonuria, has gradually become a part of countries’ national health policies as an important public health initiative to prevent disability and death.

• #1 Improving the diagnosis and treatment of inherited metabolic diseases – Pacific Northwest Research Institute

  https://pnri.org/dudley-lab/improving-the-diagnosis-and-treatment-of-inherited-metabolic-diseases/

  The Dudley Lab is applying these methods to a several metabolic diseases, including a set of rare diseases called urea cycle disorders (UCDs). […] Despite the availability of potentially lifesaving interventions such as dialysis and nitrogen scavenging drugs to reduce ammonia levels, only ~60% of early onset patients survive the neonatal period, 19% of these die within the first year of life, and most survivors have neurological damage. […] Whole exome or genome sequencing has the potential to substantially increase the positive impact of newborn screening, and pilot programs are currently evaluating its real-world implementation. By providing quantitative data on the functional impact of thousands of variants, the labs results are filling critical unmet needs that will improve the diagnosis and treatment of these devastating diseases.

• #1 Five questions about metabolic disorders – Metabolic disorders at the heart of Radio 3FM Serious Request – Radboudumc

  https://www.radboudumc.nl/en/news-items/2024/five-questions-about-metabolic-disorders

  In the Netherlands, the United for Metabolic Diseases (UMD) network of experts and patients is conducting extensive research into treatments for metabolic disorders. The goal is to treat 50% of metabolic disorders within 10 years. […] Research into gene therapy, which involves repairing DNA errors, is another promising development. Van der Meijden adds: Gene therapies are advancing in other disorders, and we hope to apply them to metabolic disorders. Several studies are underway, and new treatments for mitochondrial disorders, such as a drug developed by Khondrion, a spin-off from Radboudumc, may offer new hope. […] The goal is to improve diagnostics, prevention, treatment, and care for patients and families dealing with inherited metabolic disorders through innovative research.

• #2 The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11707409/

  Evaluating the effectiveness of these therapies for IEMs is challenging due to limited numbers of patients, geographical dispersion, and clinical diversity. […] The Treatable ID app, encompassing 116 IEMs causally linked to intellectual developmental disability (IDD) and amenable to therapy, has been downloaded over 10000 times, illustrating the widespread interest in accessible treatment-related data. […] The Treatabolome project aims to collect and freely provide information on gene-specific and variant-specific treatments for rare diseases. […] This initiative seeks to facilitate the identification of treatable IEMs for clinicians, and our objective is to provide immediate and readily accessible information on available therapies. […] Rapid diagnosis is pivotal in preventing irreversible damage.

• #2 Inherited Metabolic Disorders: Types, Signs, Causes & Treatment

  https://www.webmd.com/a-to-z-guides/inherited-metabolic-disorder-types-and-treatments

  Limited treatments are available for inherited metabolic disorders. The essential genetic defect causing the condition cant be corrected with the technology we have right now. Instead, treatments try to work around the problem with metabolism. […] There are presently therapies used for some of the inherited metabolic disorders that are quite efficacious, including medications and dietary therapy, and can help to varying degrees of effect depending on the particular disorder, Tramontana says. […] But, he continues, many of these disorders have no treatment, and for those that do, such treatments may not have much evidence to support their use. […] Treatments for genetic metabolic disorders follow a few general principles: Reduce or eliminate intake of any food or drug that cant be metabolized properly. Replace the enzyme or other chemical that is missing or inactive to restore metabolism to as close to normal as possible. Remove toxic products of metabolism that build up due to the metabolic disorder.

• #2 Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01727-2

  The different types of treatment as defined in Table 1A are shown per disorder in Table 3. Nutritional therapy was the most frequently used treatment strategy (32%), followed by pharmacological therapy 22%, vitamin and trace element substitution 22%, solid organ transplantation 8%, hematopoietic stem cell transplant 4%, enzyme replacement therapy 3%, gene-based therapy 2% and other therapy 7% (multiple treatments per disease entity were possible). […] Treatment prevented, halted, or slowed clinical deterioration in 62%, improved neurological manifestations (incl. neuro-imaging) in 47%, systemic manifestations in 44% and psychomotor/cognitive development/IQ in 37%; it prevented acute metabolic decompensation in 30%, improved seizure/epilepsy control in 22% and improved behavioural/psychiatric disturbance(s) in 21%.

• #2 Dietary Treatment For Metabolic Disease

  https://www.medschool.lsuhsc.edu/genetics/louisiana_genetics_and_hereditary_health_care_dietary_treatment.aspx

  Diet is the primary – and often the only – treatment. […] The principles are the same. Food providing the substance that accumulates at the blocked pathway is restricted so that harmful amounts won’t build up. […] Dietary treatment of PKU begins with limiting the amount of phenylalanine going into the blocked pathway. […] A special metabolic formula must also be included in the diet. […] Good dietary treatment of PKU means maintaining that perfect balance of phenylalanine, protein, and calories that supports normal growth and health, but doesn’t cause harm. […] The success of treatment can be monitored by regularly measuring phenylalanine levels in the blood. […] Compliance with the restrictions of metabolic diets is often a struggle. […] Dietary treatment is successful for many metabolic diseases that could not be treated even 10 years ago, and can make it possible for people with metabolic disease to live normal, healthy lives. […] For now, diet is the medical treatment, and should be followed with care throughout life.

• #2 Metabolic Disorders | IU Health

  https://iuhealth.org/find-medical-services/metabolic-disorders

  IU Health physicians will work with you and your primary care physicians to design an appropriate treatment plan. They will educate you and your family about the disease and its genetic basis, and treatment. They provide long-term care and support in managing metabolic diseases. […] Treatment options include: Genetic counseling. […] Specialized or restrictive diets play a key role in treating metabolic disorders. […] Some metabolic conditions require expensive foods. […] A medicine for PKU helps your body make the most use of remaining enzyme function that breaks down the phenylalanine in protein. […] Physicians and researchers at IU Health investigate the causes of and treatments for metabolic disorders.

• #2 The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11707409/

  Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. […] A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment. This study aimed to identify all treatable IEMs through a scoping literature review, followed by data extraction and analysis according to the Treatabolome principles. […] The most common treatment strategies were pharmacological therapy (34%), nutritional therapy (34%), and vitamin and trace element supplementation (12%). […] Presently, drug repurposing is gaining increasing importance. […] Gene therapies (e.g., hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy) and RNA therapies (e.g., volanesorsen in lipoprotein lipase deficiency) are emerging as promising therapeutic interventions for patients with IEMs.

• #2 Gene Therapy for Inherited Metabolic Diseases

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8518100/

  Over the last two decades, gene therapy has been successfully translated to many rare diseases. […] Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a disease-changing therapeutic option for these patients. […] In the past 20 years, gene therapy has emerged as a disease-changing treatment for these disorders. […] Gene therapy had driven fantastic hope in the mid-1990s when addressing severe combined immunodeficiency (SCID) due to deficiency of the enzyme adenosine deaminase (ADA-SCID). […] Subsequently, the research focused on safer delivery vectors and successful results have currently been reported for various inherited rare diseases such as Lebers congenital amaurosis, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, haemophilia B and many other IMDs, leading to first market authorisations in Europe and in the USA in 2012 and 2017, respectively.

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