Materiały źródłowe

• #1 Diagnosis and management of glutaric aciduria type I – revised recommendations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3109243/

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. […] It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. […] Therefore, GA-I is now considered to be a treatable condition. […] The aim of newborn and high-risk screening is to reduce the incidence of neurological disease. […] Dietary treatment in combination with carnitine and emergency treatment has been demonstrated to be effective in preventing neurological disease. […] The results of this study are supported by the highest level of evidence available regarding GA-I (i.e., 2++), and confirm previous observations suggesting that emergency treatment is the most important component of this treatment strategy.

• #2 Practical aspects of therapy for glutaric aciduria type 1 | CoLab

  https://colab.ws/articles/10.17650%2F2222-8721-2021-11-4-12-25

  Treatment of many of the diseases in the panel of expanded newborn screening includes dietary therapy. Glutaric aciduria type 1 (GA1) is a hereditary disorder caused by mutations in the gene GCDH, encoding glutaryl-CoA dehydrogenase, an enzyme in the amino acid metabolic pathways. The recommended treatment approaches for GA1 are the prescription of specialized nutrition products, levocarnitine, and symptomatic management. […] In 2021, clinical guidelines for the treatment of this rare disease were published in the Russian Federation. To provide for the timely treatment, it is essential for a practitioner involved in the care of patients with such a rare disorder as GA1 to have the knowledge of the principles of management, as well as practical algorithms for diet calculation. The article gives a detailed case-based description of management during metabolic decompensation and the choice of dietary therapy for GA1 patients of different age groups.

• #3 Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33069577/

  Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in 80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kgday), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kgday) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet.

• #4

  https://link.springer.com/article/10.1007/s10545-011-9289-5

  Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. […] It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. […] Therefore, GA-I is now considered to be a treatable condition. […] The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline.

• #5 Glutaric aciduria | MedLink Neurology

  https://www.medlink.com/articles/glutaric-aciduria

  In a neonatally screened population, quality of therapy becomes the major predictor of neurologic outcome and survival. […] The principal therapy of glutaric aciduria type I comprises (1) a low lysine diet, (2) carnitine supplementation (50 to 100 mg/kg/day), and (3) prevention or reversal of catabolic state by intermittent emergency treatment. […] Treatment should be initiated and patients should be followed by an interdisciplinary team of metabolic specialists, dieticians, psychologists, neurologists, physical therapists, and occupational therapists. […] Intensified emergency treatment should be started without delay and before neurologic symptoms occur during each putatively threatening episode, such as infectious disease. […] A meta-analysis comparing screened and unscreened cohorts has confirmed the major impact of newborn screening for glutaric aciduria type I on individual health, but at the same time has highlighted that therapeutic quality becomes a major predictor of neurologic outcome in screened populations.

• #6 Diagnosis and management of glutaric aciduria type I – revised recommendations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3109243/

  Statement #6. Metabolic treatment should be implemented by an interdisciplinary team that includes metabolic pediatricians, dietitians, and nurses. […] Statement #8. L-Carnitine should be supplemented in patients with glutaric aciduria type I and should be continued lifelong. […] Emergency treatment should start without delay and should be performed aggressively during febrile illness, surgery and immunization within the vulnerable period for acute encephalopathic crises (up to age 6 years).

• #7 Glutaric aciduria | MedLink Neurology

  https://www.medlink.com/articles/glutaric-aciduria

  In a neonatally screened population, quality of therapy becomes the major predictor of neurologic outcome and survival. […] The principal therapy of glutaric aciduria type I comprises (1) a low lysine diet, (2) carnitine supplementation (50 to 100 mg/kg/day), and (3) prevention or reversal of catabolic state by intermittent emergency treatment. […] Treatment should be initiated and patients should be followed by an interdisciplinary team of metabolic specialists, dieticians, psychologists, neurologists, physical therapists, and occupational therapists. […] Intensified emergency treatment should be started without delay and before neurologic symptoms occur during each putatively threatening episode, such as infectious disease. […] A meta-analysis comparing screened and unscreened cohorts has confirmed the major impact of newborn screening for glutaric aciduria type I on individual health, but at the same time has highlighted that therapeutic quality becomes a major predictor of neurologic outcome in screened populations.

• #8 What is glutaric aciduria type 1?

  https://www.medicalnewstoday.com/articles/glutaric-aciduria-type-1

  According to a 2020 study, early diagnosis and treatment of GA1 can prevent potential complications while supporting typical growth and psychomotor development. […] The guidelines for managing and treating GA1 involve metabolic maintenance treatment. This consists of working closely with the metabolic team, following a low protein diet, and taking medications to reduce glutaric acid levels. […] A specialist metabolic dietitian will tailor a low protein diet. In particular, this diet will reduce the amounts of amino acids, such as lysine and tryptophan, that a person consumes. A dietitian may also provide lysine-free, tryptophan-reduced amino acid formulas to ensure adequate intake of essential amino acids, minerals, and vitamins. […] In addition to dietary treatment, a dietitian may recommend supplements such as L-carnitine, riboflavin, or coenzyme Q10.

• #9 Glutaric aciduria type 1

  https://www.nhs.uk/conditions/glutaric-aciduria/

  If GA1 is diagnosed, treatment can be given straight away to reduce the risk of serious complications. […] With early diagnosis and the correct treatment, the majority of children with GA1 are able to live normal, healthy lives. However, treatment for GA1 must be continued for life. […] Children diagnosed with GA1 are referred to a specialist metabolic dietitian and given a low-protein diet. This is tailored to reduce the amount of amino acids your baby receives, especially lysine and tryptophan. […] Your child will be prescribed a medication called L-carnitine, which helps to clear some of the excess glutaric acid. […] If your baby develops an infection, such as a high temperature or cold, their risk of having a metabolic crisis increases. It’s possible to reduce the risk by changing to an emergency diet while they’re ill.

• #10 Glutaric aciduria type 1 (GA-1)

  https://www.nutricia.com/specialize/iem/ga1.html

  GA1 is effectively managed by lifelong adherence to a low lysine diet. The goal of adhering to a low lysine for GA1 diet is to provide the optimal intake of lysine as it is an essential amino acid to ensure good growth but avoid excess intake of this amino acid which can be harmful. […] The principles of dietary management of GA1 consists of the following: Intake of controlled amounts of foods naturally high in lysine, individually calculated by a dietitian, Lifelong oral supplementation of l-carnitine, an amino acid essential, Consumption of lysine free, tryptophan reduced and arginine enriched protein substitutes as medically prescribed to ensure requirements for essential amino acids, minerals, vitamins and trace elements are met. […] Lifelong monitoring to ensure optimal amino acid blood levels. The medical team will regularly assess blood samples and recommend dietary adjustments accordingly and as nutritional requirements change depending on the life stage. […] The combination of the all of the above, closely monitored and adjusted according to changing nutritional needs ensures all the essential nutrients are provided to support optimal growth, development and physical health.

• #11 Inconsistencies in the Nutrition Management of Glutaric Aciduria Type 1: An International Survey

  https://www.mdpi.com/2072-6643/12/10/3162

  Glutaric aciduria type 1 (GA-1) is a cerebral organic aciduria characterized by striatal injury and progressive movement disorder. Nutrition management shifted from a general restriction of intact protein to targeted restriction of lysine and tryptophan. […] Current therapeutic strategies focus on limiting the accumulation of metabolites through aggressive management of illness to limit catabolism and the use of carnitine to enhance detoxification of glutaryl-CoA and prevent a secondary carnitine deficiency. Similarly, dietary-based treatments reduce precursor amino acids lysine and tryptophan and subsequently decrease the accumulation of glutaric acid and 3-hydroxyglutaric acid. […] Despite these concerns, dietary-based therapies remain central to the treatment of patients with GA-1. […] Recent guidelines advocate for a low-lysine diet through the use of lysine-free, tryptophan-reduced amino acid supplements (medical foods). […] The revised guidelines strongly recommend a low lysine diet with amino acid-based medical foods up to age six years. After age six years, the recommendation is to transition to an individualized age-appropriate “protein-controlled” diet.

• #12

  https://link.springer.com/article/10.1007/s10545-011-9289-5

  Timely diagnosis and start of treatment, i.e., before irreversible neurological symptoms occur, results in a better outcome than start of treatment after the onset of neurological disease. […] Metabolic treatment should be implemented by an interdisciplinary team that includes metabolic pediatricians, dietitians, and nurses. […] Most patients remain asymptomatic if treatment is started in the newborn period. […] Dietary treatment in combination with carnitine and emergency treatment has been demonstrated to be effective in preventing neurological disease. […] The use of a low lysine diet (i.e., reducing lysine intake to a safe requirement) with or without additional administration of lysine-free, tryptophan-reduced amino acids supplements should be used for dietary treatment, in particular in asymptomatic patients up to age 6 years.

• #13 Glutaric Aciduria Type 1 – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/glutaric-aciduria-type-1/

  GA1 is managed with the following special diet and medication: A protein-restricted diet, A protein substitute, Carnitine medication. […] In GA1, it is important that enough protein is given for growth… but not too much as toxic chemicals will be made. […] Protein substitute is essential for metabolic control. It will help to meet your baby’s protein, energy, vitamin and mineral requirements. It is available on prescription. […] During any childhood illness, an emergency regimen is given. Illnesses can cause catabolism or protein breakdown. This will lead to a build-up of glutaric acid and cause a metabolic crisis. […] During illness, you should: Stop all protein in food and drink, Start the emergency regimen. This is made up of protein substitute and glucose polymer, Use carnitine medication as prescribed, Phone your metabolic team. […] It is imperative that emergency feeds are started promptly and there are no delays in management. […] With good management, severe movement problems can be prevented in the majority of children.

• #14 Glutaric aciduria type 1 (GA-1)

  https://www.nutricia.com/specialize/iem/ga1.html

  GA1 is effectively managed by lifelong adherence to a low lysine diet. The goal of adhering to a low lysine for GA1 diet is to provide the optimal intake of lysine as it is an essential amino acid to ensure good growth but avoid excess intake of this amino acid which can be harmful. […] The principles of dietary management of GA1 consists of the following: Intake of controlled amounts of foods naturally high in lysine, individually calculated by a dietitian, Lifelong oral supplementation of l-carnitine, an amino acid essential, Consumption of lysine free, tryptophan reduced and arginine enriched protein substitutes as medically prescribed to ensure requirements for essential amino acids, minerals, vitamins and trace elements are met. […] Lifelong monitoring to ensure optimal amino acid blood levels. The medical team will regularly assess blood samples and recommend dietary adjustments accordingly and as nutritional requirements change depending on the life stage. […] The combination of the all of the above, closely monitored and adjusted according to changing nutritional needs ensures all the essential nutrients are provided to support optimal growth, development and physical health.

• #15 Diagnosis and management of glutaric aciduria type I – revised recommendations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3109243/

  Statement #6. Metabolic treatment should be implemented by an interdisciplinary team that includes metabolic pediatricians, dietitians, and nurses. […] Statement #8. L-Carnitine should be supplemented in patients with glutaric aciduria type I and should be continued lifelong. […] Emergency treatment should start without delay and should be performed aggressively during febrile illness, surgery and immunization within the vulnerable period for acute encephalopathic crises (up to age 6 years).

• #16

  https://www.omim.org/entry/231670

  Heringer et al. (2010) summarized the guidelines published by Kolker et al. (2007) for the management of glutaryl-CoA dehydrogenase deficiency. Recommendations included a lysine-restricted diet to reduce the accumulation of the neurotoxic metabolites glutaric acid, 3-hydroxyglutaric acid, and glutaryl-CoA deriving from the precursor amino acid lysine; the supplementation of carnitine to prevent secondary carnitine depletion, to facilitate production of the nontoxic C5DC, and to replenish the intracellular free coenzyme A pool; and the intermittent and stepwise intensification of metabolic treatment using a high-calorie, low- or no-protein emergency treatment protocol during putatively threatening episodes such as infectious disease to prevent striatal injury. […] Strauss et al. (2020) concluded that neonatal diagnosis coupled with management with a lysine-free, arginine-rich formula and emergency IV infusions in the first 2 years of life is effective and safe.

• #17

  https://link.springer.com/article/10.1007/s10545-011-9289-5

  L-Carnitine should be supplemented in patients with glutaric aciduria type I and should be continued lifelong. […] Emergency treatment should start without delay and should be performed aggressively during febrile illness, surgery and immunization within the vulnerable period for acute encephalopathic crises (up to age 6 years).

• #18

  https://journals.lww.com/annalsofian/fulltext/2012/15010/glutaric_aciduria_type_i__a_treatable.9.aspx

  Management includes the prevention or reversal of a catabolic state by administration of a high-energy intake (plus insulin to control for hyperglycemia if required); reduction of GA and 3-OH-GA production by transient reduction or omission of natural protein for 24-48 h; amplification of physiological detoxification mechanisms and prevention of secondary carnitine depletion by L-carnitine supplementation (doubling the maintenance dose of 100 mg/kg day) and maintenance of normal fluid, electrolytes and pH status via enteral of IV fluids. […] Timely diagnosis and start of treatment, i.e. before an acute encephalopathic crisis, is likely to result in a better outcome than diagnosis and start of treatment after the onset of neurological disease.

• #19 Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33069577/

  Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in 80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kgday), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kgday) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet.

• #20 Glutaric aciduria type 1 – Wikipedia

  https://en.wikipedia.org/wiki/Glutaric_aciduria_type_1

  Correction of secondary carnitine depletion. Like many other organic acidemias, GA1 causes carnitine depletion. Whole-blood carnitine can be raised by oral supplementation. However, this does not significantly change blood concentrations of glutarylcarnitine or esterified carnitine, suggesting that oral supplementation is suboptimal in raising tissue levels of carnitine. Clinical nutrition researchers have likewise concluded that oral carnitine raises plasma levels but does not affect those in muscles, where most of it is stored and used. […] In contrast, regular intravenous infusions of carnitine cause distinct clinical improvements: „decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake.”

• #21 Diagnosis and management of glutaric aciduria type I – revised recommendations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3109243/

  Statement #6. Metabolic treatment should be implemented by an interdisciplinary team that includes metabolic pediatricians, dietitians, and nurses. […] Statement #8. L-Carnitine should be supplemented in patients with glutaric aciduria type I and should be continued lifelong. […] Emergency treatment should start without delay and should be performed aggressively during febrile illness, surgery and immunization within the vulnerable period for acute encephalopathic crises (up to age 6 years).

• #22 Glutaric aciduria | MedLink Neurology

  https://www.medlink.com/articles/glutaric-aciduria

  In a neonatally screened population, quality of therapy becomes the major predictor of neurologic outcome and survival. […] The principal therapy of glutaric aciduria type I comprises (1) a low lysine diet, (2) carnitine supplementation (50 to 100 mg/kg/day), and (3) prevention or reversal of catabolic state by intermittent emergency treatment. […] Treatment should be initiated and patients should be followed by an interdisciplinary team of metabolic specialists, dieticians, psychologists, neurologists, physical therapists, and occupational therapists. […] Intensified emergency treatment should be started without delay and before neurologic symptoms occur during each putatively threatening episode, such as infectious disease. […] A meta-analysis comparing screened and unscreened cohorts has confirmed the major impact of newborn screening for glutaric aciduria type I on individual health, but at the same time has highlighted that therapeutic quality becomes a major predictor of neurologic outcome in screened populations.

• #23 Glutaric Aciduria Type 1 – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/glutaric-aciduria-type-1/

  GA1 is managed with the following special diet and medication: A protein-restricted diet, A protein substitute, Carnitine medication. […] In GA1, it is important that enough protein is given for growth… but not too much as toxic chemicals will be made. […] Protein substitute is essential for metabolic control. It will help to meet your baby’s protein, energy, vitamin and mineral requirements. It is available on prescription. […] During any childhood illness, an emergency regimen is given. Illnesses can cause catabolism or protein breakdown. This will lead to a build-up of glutaric acid and cause a metabolic crisis. […] During illness, you should: Stop all protein in food and drink, Start the emergency regimen. This is made up of protein substitute and glucose polymer, Use carnitine medication as prescribed, Phone your metabolic team. […] It is imperative that emergency feeds are started promptly and there are no delays in management. […] With good management, severe movement problems can be prevented in the majority of children.

• #24 What is glutaric aciduria type 1?

  https://www.medicalnewstoday.com/articles/glutaric-aciduria-type-1

  The medical team will provide detailed instructions for emergency treatment. The emergency regimen varies slightly between children and adults but involves administering a solution rich in glucose or dextrose to provide energy and help limit the buildup of harmful substances in the brain and body. […] Treatment for GA1 involves following a low protein diet and consuming special formulas to ensure sufficient nutritional intake.

• #25

  https://www.gov.uk/government/publications/ga1-suspected-description-in-brief/glutaric-aciduria-type-1-ga1-detailed-information

  The emergency regimen is made up of GA1 specialist infant formula and glucose polymer powder. It is given regularly, day and night, to provide energy and help limit the build-up of harmful substances in the brain and body. […] Your GP will be asked to prescribe the glucose polymer powder. […] With treatment, the outcome is usually very good and most children will avoid any long-term health problems. The risk of severe brain damage is low after the age of 6 years. Dietary treatment may be relaxed in later childhood but the emergency regimen and L-carnitine will need to be continued.

• #26 Glutaric Aciduria Type 1 – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/glutaric-aciduria-type-1/

  GA1 is managed with the following special diet and medication: A protein-restricted diet, A protein substitute, Carnitine medication. […] In GA1, it is important that enough protein is given for growth… but not too much as toxic chemicals will be made. […] Protein substitute is essential for metabolic control. It will help to meet your baby’s protein, energy, vitamin and mineral requirements. It is available on prescription. […] During any childhood illness, an emergency regimen is given. Illnesses can cause catabolism or protein breakdown. This will lead to a build-up of glutaric acid and cause a metabolic crisis. […] During illness, you should: Stop all protein in food and drink, Start the emergency regimen. This is made up of protein substitute and glucose polymer, Use carnitine medication as prescribed, Phone your metabolic team. […] It is imperative that emergency feeds are started promptly and there are no delays in management. […] With good management, severe movement problems can be prevented in the majority of children.

• #27

  https://journals.lww.com/annalsofian/fulltext/2012/15010/glutaric_aciduria_type_i__a_treatable.9.aspx

  Management includes the prevention or reversal of a catabolic state by administration of a high-energy intake (plus insulin to control for hyperglycemia if required); reduction of GA and 3-OH-GA production by transient reduction or omission of natural protein for 24-48 h; amplification of physiological detoxification mechanisms and prevention of secondary carnitine depletion by L-carnitine supplementation (doubling the maintenance dose of 100 mg/kg day) and maintenance of normal fluid, electrolytes and pH status via enteral of IV fluids. […] Timely diagnosis and start of treatment, i.e. before an acute encephalopathic crisis, is likely to result in a better outcome than diagnosis and start of treatment after the onset of neurological disease.

• #28 Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33069577/

  Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in 80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kgday), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kgday) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet.

• #29 Perioperative Management of a Patient With Glutaric Aciduria | Hakim | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2096/1539

  Glutaric aciduria type-1 (GA-1) is an autosomal recessive metabolic disorder due to the deficiency of the enzyme, glutaryl-CoA dehydrogenase. […] The progressive neurologic effects of the disorder frequently lead to spasticity and orthopedic deformities requiring surgical and anesthetic care. […] Routine newborn screening has allowed early diagnosis with the institution of dietary restriction, carnitine and riboflavin supplementation, and treatment of acute encephalopathic crisis, thereby allowing for more normal development. […] Despite these therapies, acute exacerbations of the disorder (encephalopathic crisis) may be triggered by infections, stress, fever, or surgery. […] Perioperative care focuses on the maintenance of normal homeostasis with provision of fluid and glucose during fasting to prevent catabolism and the release of endogenous amino acids.

• #30 Impact of newborn screening and quality of therapy on the neurological outcome in glutaric aciduria type 1: a meta-analysis | Genetics in Medicine

  https://www.nature.com/articles/s41436-020-00971-4

  Patients not following MT guideline recommendations showed a trend for increased relative risk (log risk ratio) for insidious onset MD compared with patients with recommended dietary treatment. […] Patients with delayed ET had an increased RR (log risk ratio) for acute onset MD compared with patients treated according to recommended ET. […] Quality of therapy becomes the major predictor of neurological outcome in a screened population of GA1.

• #31 Simplified Approach to Glutaric Acidurias: A Mini-Review

  https://www.rarediseasesjournal.com/articles/simplified-approach-to-glutaric-acidurias-a-minireview.html

  Glutaric acidurias are a group of OADs which have three major types with different genetic mutations affecting different metabolic enzymes and all three having an autosomal recessive inheritance. […] Treatment for IMDs depends on the type and severity of the disease, and since there are so many types of IMDs, treatments may vary from dietary restrictions and supplements to liver transplants. […] The early diagnosis of GA-I is essential, since the metabolic symptoms can be usually prevented by carnitine supplementation and a diet that is low in lysine and tryptophan to reduce glutaric acid production, and also may include supplementation with L-carnitine, riboflavin. […] The conventional treatment of GA-II, including a protein- and fat-restricted, carbohydrate-rich diet, and riboflavin, glycine, and L-carnitine supplementation, may be effective in mildly affected patients, however, in some cases results can be disappointing. […] Treatment with D,L-3-hydroxybutyrate is safe and effective and not associated with any notable adverse side-effects.

• #32 Glutaric acidemia type I | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/glutaric-acidemia-type-i

  It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition. […] Treatments may include the following: […] Diet of special formulas or foods […] Riboflavin (vitamin B-2) supplements (in some cases) […] L-carnitine supplements (in some cases) […] People with glutaric acidemia type I must be very careful during illnesses that cause poor appetite, vomiting, or diarrhea. During these illnesses, people with this condition may need emergency care and intravenous (IV) treatments. […] Children who receive early and ongoing treatment for glutaric acidemia type I can have healthy growth and development.

• #33 Indian Pediatrics – Brief Reports

  https://www.indianpediatrics.net/oct2001/oct-1148-1154.htm

  Baclofen, a GABA analog is used to alleviate neurological symptoms. […] Early institution of therapy can provide gratifying results. It halts the further progression of the neurological disability in most patients. Its institution in the pre-symptomatic phase is known to prevent the onset of symptoms and may lead to normal development. […] As with other inherited disorders, genetic counselling and prenatal diagnosis are important aspects of management.

• #34 Glutaric Aciduria Type I Diagnosis Case with Normal Glutaryl Carnitine and Urine Organic Acid Analysis – The Journal of Pediatric Research

  https://jpedres.org/articles/glutaric-aciduria-type-i-diagnosis-case-with-normal-glutaryl-carnitine-and-urine-organic-acid-analysis/doi/jpr.85530

  Glutaric aciduria Type I (GA-I) is a rare inherited metabolic disease, deficiency of glutaryl-CoA dehydrogenase results in accumulation of the putatively neurotoxic metabolites glutaric and 3-hydroxyglutaric acid (GA, 3-OH-GA) in body tissues, particularly within the brain. […] The major therapeutic principles GA-I are; the reduction of glutaryl CoA, GA, 3-OH-GA using low lysine diet and prevention of secondary carnitine deficiency. […] The patient was treated with levodopa and trihexyphenidyl and lysine-restricted diet. […] Basic metabolic treatment of GA-I is using low lysine diet for reduction of glutaryl-CoA, GA and 3-OH-GA and carnitine supplementation to prevent carnitine depletion. […] Dietary treatment in combination with carnitine and emergency treatment has been shown to be effective in preventing neurological disease. […] We treated our patient with low lysine diet and carnitine supplementation. […] GA-I is a treatable inborn metabolic disorder.

• #35 Perioperative Management of a Patient With Glutaric Aciduria | Hakim | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2096/1539

  Glutaric aciduria type-1 (GA-1) is an autosomal recessive metabolic disorder due to the deficiency of the enzyme, glutaryl-CoA dehydrogenase. […] The progressive neurologic effects of the disorder frequently lead to spasticity and orthopedic deformities requiring surgical and anesthetic care. […] Routine newborn screening has allowed early diagnosis with the institution of dietary restriction, carnitine and riboflavin supplementation, and treatment of acute encephalopathic crisis, thereby allowing for more normal development. […] Despite these therapies, acute exacerbations of the disorder (encephalopathic crisis) may be triggered by infections, stress, fever, or surgery. […] Perioperative care focuses on the maintenance of normal homeostasis with provision of fluid and glucose during fasting to prevent catabolism and the release of endogenous amino acids.

• #36 Perioperative Management of a Patient With Glutaric Aciduria | Hakim | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2096/1539

  During NPO times, given the potential impact of catabolism and the risks of hypoglycemia, intravenous fluids and dextrose should be provided to meet maintenance needs. […] Perioperatively, routine medications including anticonvulsant agents, carnitine, and riboflavin should be continued. […] Given the significant comorbid sequelae of GA-1, there are several specific perioperative implications which may significantly impact the risk for perioperative morbidity and mortality. […] Anesthetic concerns include the potential for metabolic derangements from the effects of prolonged propofol infusions on mitochondrial fatty acid metabolism and the potential for prolonged effects of neuromuscular blocking agents. […] The preoperative assessment of end-organ impairment by the primary disease process and close postoperative monitoring are mandatory for the effective perioperative care of these patients.

• #37 Perioperative Management of a Patient With Glutaric Aciduria | Hakim | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2096/1539

  During NPO times, given the potential impact of catabolism and the risks of hypoglycemia, intravenous fluids and dextrose should be provided to meet maintenance needs. […] Perioperatively, routine medications including anticonvulsant agents, carnitine, and riboflavin should be continued. […] Given the significant comorbid sequelae of GA-1, there are several specific perioperative implications which may significantly impact the risk for perioperative morbidity and mortality. […] Anesthetic concerns include the potential for metabolic derangements from the effects of prolonged propofol infusions on mitochondrial fatty acid metabolism and the potential for prolonged effects of neuromuscular blocking agents. […] The preoperative assessment of end-organ impairment by the primary disease process and close postoperative monitoring are mandatory for the effective perioperative care of these patients.

• #38

  https://grantome.com/grant/NIH/R21-HD088775-02

  In this project, the investigators propose to develop novel treatment options for glutaric aciduria type 1 (GA1; MIM 231670). […] GA1 is considered a treatable disorder and therefore included in newborn screening programs in many countries. However, current treatment consists of dietary intervention, carnitine supplementation, and emergency treatment. […] These limitations demonstrate the need for novel therapeutic options with improved efficacy and convenience. The investigators hypothesize that by using inhibitors upstream in the lysine degradation pathway, accumulation of neurotoxic glutaric acid and 3-hydroxyglutaric acid in GA1 can be diverted into more tolerable metabolites. […] Therefore, the investigators propose that DHTKD1 is an excellent target for treatment of GA1. […] Thus the overall objective of this proposal is to identify novel small-molecule inhibitor leads for DHTKD1 suitable for future medicinal chemistry optimization.

• #39 Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement | Gene Therapy

  https://www.nature.com/articles/s41434-023-00428-8

  Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. […] Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.

• #40 Promising study suggests that AAV-based gene therapy can treat glutaric aciduria type I | KeAi Publishing

  https://www.keaipublishing.com/en/journals/fundamental-research/news/promising-study-suggests-that-aav-based-gene-therapy-can-treat-glutaric-aciduria-type-i/

  Glutaric aciduria type I (GA-I) is an inherited disease caused by a mutation of the glutaryl-CoA dehydrogenase (GCDH) gene. […] There is no available cure, and, without proper treatment, life expectancy is just 2-3 years. With treatment, such as diet control, carnitine supplements and medical care for acute attacks, some disease progression can be managed. […] The research team chose to go the AAV route as it has proven to be an effective treatment for a variety of genetic disorders. […] The next step is to move this forward to become a marketed drug and an investigator-initiated clinical trial is already underway. Meanwhile, we are so pleased that this project has received a Rare Pediatric Disease Designation (RPDD) from the Food and Drug Administration (FDA). This designation is designed to support rare diseases in children with unmet needs. Its purpose is to stimulate the development of new drugs for these conditions by incentivizing researchers to get FDA approval of the treatments.

• #41

  https://www.jci.org/articles/view/31617

  Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. […] Current therapy for GA-I includes dietary lysine restriction, carnitine supplementation, and emergency treatment of intercurrent illness including intravenous glucose. […] Unfortunately, one-third of affected children, prospectively identified by newborn screening, do not respond to therapy and experience striatal degeneration despite careful clinical management. […] We propose that a similar mechanism regulates lysine utilization in the immature brain. […] Combined homoarginine and glucose treatment may provide the best protection by reducing the substrate and the drive for glutaric acid production.

• #42

  https://www.jci.org/articles/view/31617

  Currently, there is no reliable marker that can be used noninvasively for predicting the risk of brain injury in human GA-I. […] The current findings provide insight into the age-dependent mechanism, treatment, and monitoring of GA-I and offer new strategies for the prediction and prevention of brain injury.

• #43 Impact of newborn screening and quality of therapy on the neurological outcome in glutaric aciduria type 1: a meta-analysis | Genetics in Medicine

  https://www.nature.com/articles/s41436-020-00971-4

  Glutaric aciduria type 1 (GA1), a rare inherited neurometabolic disorder, results in a complex movement disorder (MD) with predominant dystonia if untreated. Implementation into newborn screening (NBS) programs and adherence to recommended therapy are thought to improve the neurological outcome. […] Metabolic treatment consisting of a low lysine diet and carnitine supplementation for maintenance treatment (MT) as well as an intermittent emergency treatment (ET) during episodes that are likely to induce catabolism such as febrile infections is recommended by a revised evidence-based guideline. […] This meta-analysis demonstrates that NBS programs for GA1 have an overall positive effect on the neurological outcome of affected individuals but their success critically depends on the quality of therapy.

• #44 Glutaric aciduria | MedLink Neurology

  https://www.medlink.com/articles/glutaric-aciduria

  The prognostically relevant event of this disease is the manifestation of striatal injury during infancy or early childhood, resulting in poor neurologic outcome and reduced life expectancy. If an infant is diagnosed at birth or before neurologic injury occurs and metabolic management is promptly initiated and follows current treatment recommendations, affected individuals with glutaric aciduria type I can have promising outcome, which is confirmed by a growing number of observational studies and a meta-analysis.

• #45

  https://www.omim.org/entry/231670

  Boy et al. (2018) evaluated clinical treatment and outcomes in 94 individuals from Germany identified between 1999 and 2016 with glutaric acidemia I, including 87 patients who were identified by newborn screening, 4 patients missed by newborn screening, and 3 women identified with GA1 because of a positive newborn screen of their unaffected child. Sixty-four patients had a high excreter phenotype and 21 patients had a low excreter phenotype. Fifty-six patients (64%) who were detected by newborn screen remained asymptomatic, 26 patients (30%) had major motor symptoms, and 5 patients (6%) had minor motor symptoms. Outcomes were assessed in association with adherence to maintenance and emergency therapy. Maintenance therapy included a low-lysine diet supplemented with a lysine-free, tryptophan-reduced, arginine-containing formula in patients up to 6 years of age, a protein-controlled diet for patients older than 6 years, and lifelong supplementation with carnitine. Emergency therapy included a carbohydrate-enriched, low- or no-protein protocol initiated during catabolic episodes (e.g., fever, vomiting). Among the patients who had presymptomatic initiation of treatment and adherence to both maintenance therapy and emergency treatment, 7% developed a movement disorder. Of the patients who did not have presymptomatic initiation of treatment, 100% had an acute onset of a movement disorder. Nonadherence to emergency treatment had the strongest impact on outcome, with patients usually developing a severe movement disorder. Patients who didn’t follow recommendations for maintenance therapy mostly had increased risk for a mild insidious onset of dystonia. Kidney function was found to decline with age regardless of neurologic phenotype.

• #46 Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0612-6

  Without neonatal initiation of treatment, 8090% of patients with glutaric aciduria type 1 (GA1) develop striatal injury during the first six years of life resulting in a complex, predominantly dystonic movement disorder. […] In contrast, most patients diagnosed by newborn screening (NBS) and treated according to guideline recommendations since neonates, remain asymptomatic. […] All patients over the age of 6 years followed a protein-controlled diet using natural protein with a low lysine content and avoiding lysine-rich food and orally supplemented carnitine. Until the age of 6 years the early diagnosed control patients received combined metabolic therapy consisting of a low-lysine diet, carnitine supplementation, and a high-caloric, low- or no-protein emergency dietary regimen during episodes likely to induce catabolism.

• #47

  https://www.omim.org/entry/231670

  Boy et al. (2018) evaluated clinical treatment and outcomes in 94 individuals from Germany identified between 1999 and 2016 with glutaric acidemia I, including 87 patients who were identified by newborn screening, 4 patients missed by newborn screening, and 3 women identified with GA1 because of a positive newborn screen of their unaffected child. Sixty-four patients had a high excreter phenotype and 21 patients had a low excreter phenotype. Fifty-six patients (64%) who were detected by newborn screen remained asymptomatic, 26 patients (30%) had major motor symptoms, and 5 patients (6%) had minor motor symptoms. Outcomes were assessed in association with adherence to maintenance and emergency therapy. Maintenance therapy included a low-lysine diet supplemented with a lysine-free, tryptophan-reduced, arginine-containing formula in patients up to 6 years of age, a protein-controlled diet for patients older than 6 years, and lifelong supplementation with carnitine. Emergency therapy included a carbohydrate-enriched, low- or no-protein protocol initiated during catabolic episodes (e.g., fever, vomiting). Among the patients who had presymptomatic initiation of treatment and adherence to both maintenance therapy and emergency treatment, 7% developed a movement disorder. Of the patients who did not have presymptomatic initiation of treatment, 100% had an acute onset of a movement disorder. Nonadherence to emergency treatment had the strongest impact on outcome, with patients usually developing a severe movement disorder. Patients who didn’t follow recommendations for maintenance therapy mostly had increased risk for a mild insidious onset of dystonia. Kidney function was found to decline with age regardless of neurologic phenotype.

• #48 Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0612-6

  Treatment however does not preclude development or progression of MR changes in late-onset or control patients, e.g. white matter changes were slightly progressive in late-onset patient p1 despite initiation of treatment and resolution of clinical symptoms and developed in control patient c5 between MRIs at 4 and 11 years. […] We hypothesize that late-onset GA1 is the result of long-term toxicity in untreated GA1 patients with a high excreting phenotype. Accordingly, differences between late onset GA1 and early treated patients might reflect the higher long-term risk of high excretors compared to low excretors and of individuals remaining undiagnosed and untreated for years, even decades.

• #49 Diagnosis and management of glutaric aciduria type I – revised recommendations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3109243/

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. […] It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. […] Therefore, GA-I is now considered to be a treatable condition. […] The aim of newborn and high-risk screening is to reduce the incidence of neurological disease. […] Dietary treatment in combination with carnitine and emergency treatment has been demonstrated to be effective in preventing neurological disease. […] The results of this study are supported by the highest level of evidence available regarding GA-I (i.e., 2++), and confirm previous observations suggesting that emergency treatment is the most important component of this treatment strategy.

• #50 Glutaric aciduria | MedLink Neurology

  https://www.medlink.com/articles/glutaric-aciduria

  The prognostically relevant event of this disease is the manifestation of striatal injury during infancy or early childhood, resulting in poor neurologic outcome and reduced life expectancy. If an infant is diagnosed at birth or before neurologic injury occurs and metabolic management is promptly initiated and follows current treatment recommendations, affected individuals with glutaric aciduria type I can have promising outcome, which is confirmed by a growing number of observational studies and a meta-analysis.

• #51

  https://link.springer.com/article/10.1007/s10545-011-9289-5

  L-Carnitine should be supplemented in patients with glutaric aciduria type I and should be continued lifelong. […] Emergency treatment should start without delay and should be performed aggressively during febrile illness, surgery and immunization within the vulnerable period for acute encephalopathic crises (up to age 6 years).

• #52 Glutaric aciduria type 1

  https://www.nhs.uk/conditions/glutaric-aciduria/

  If GA1 is diagnosed, treatment can be given straight away to reduce the risk of serious complications. […] With early diagnosis and the correct treatment, the majority of children with GA1 are able to live normal, healthy lives. However, treatment for GA1 must be continued for life. […] Children diagnosed with GA1 are referred to a specialist metabolic dietitian and given a low-protein diet. This is tailored to reduce the amount of amino acids your baby receives, especially lysine and tryptophan. […] Your child will be prescribed a medication called L-carnitine, which helps to clear some of the excess glutaric acid. […] If your baby develops an infection, such as a high temperature or cold, their risk of having a metabolic crisis increases. It’s possible to reduce the risk by changing to an emergency diet while they’re ill.

• #53 Newborn screening information for glutaric acidemia type I | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/glutaric-acidemia-type-i

  L-carnitine is another natural supplement that your babys doctor might recommend. L-carnitine helps your babys body get rid of harmful wastes. […] If glutaric acidemia, type 1 (GA-1) is treated early and throughout life, your baby can have healthy growth and development. […] It is important to screen for and treat GA-1 early. If GA-1 is untreated, it can lead to seizures, coma, or permanent brain damage.

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