Materiały źródłowe

• #1 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. […] Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria caused by glutaryl-CoA dehydrogenase (GCDH) deficiency with an estimated overall prevalence of 1 in 100,000 newborns. […] The initial progression of clinical symptoms in cases of GA-I is slow; hence GA-I is frequently left undiagnosed until an acute metabolic crisis occurs. A child suffering from GA-I usually presents with macrocephaly which is found in 75% of GA-I patients during infancy. […] Clinical presentations with acute encephalopathic crises are seen mostly between 6 and 18 months and induced by febrile illness, fasting, or immunization. Dystonia and extrapyramidal symptoms such as athetosis, seizures, and intellectual disability may be the other signs in GA-I. However some patients with GA-I remain asymptomatic, even in the adulthood. […] 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.

• #2 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. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] Early clinical diagnosis is hampered by the lack of characteristic or even pathognomonic signs and symptoms before an encephalopathic crisis. Macrocephaly is found in 75% of patients during infancy, but is non-specific. Therefore GA-I has been included in the disease panel of newborn screening in some countries.

• #3 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. […] Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria caused by glutaryl-CoA dehydrogenase (GCDH) deficiency with an estimated overall prevalence of 1 in 100,000 newborns. […] The initial progression of clinical symptoms in cases of GA-I is slow; hence GA-I is frequently left undiagnosed until an acute metabolic crisis occurs. A child suffering from GA-I usually presents with macrocephaly which is found in 75% of GA-I patients during infancy. […] Clinical presentations with acute encephalopathic crises are seen mostly between 6 and 18 months and induced by febrile illness, fasting, or immunization. Dystonia and extrapyramidal symptoms such as athetosis, seizures, and intellectual disability may be the other signs in GA-I. However some patients with GA-I remain asymptomatic, even in the adulthood. […] 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.

• #4 Glutaric acidemia type I | Newborn Screening

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

  Signs of glutaric acidemia type I can vary widely. Without treatment, they most often appear between 4 months and 2 years of age. […] Signs of the condition may include the following: Poor appetite, Sleeping longer or more often, Large head (macrocephaly), Difficulty moving, Twitches or spasms, Floppy arms and legs (hypotonia), Delayed growth, Developmental delays. […] If untreated, this damage leads to the signs and symptoms of the condition. In severe cases, this condition can result in coma, brain damage, or death unless treated early.

• #5 Glutaric aciduria type 1 – Wikipedia

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

  The severity of glutaric acidemia type 1 varies widely; some individuals are only mildly affected, while others suffer severe problems. […] Babies with glutaric acidemia type 1 often are born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. […] Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). […] Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. […] A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises, usually with following brain damage.

• #6 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. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] Early clinical diagnosis is hampered by the lack of characteristic or even pathognomonic signs and symptoms before an encephalopathic crisis. Macrocephaly is found in 75% of patients during infancy, but is non-specific. Therefore GA-I has been included in the disease panel of newborn screening in some countries.

• #7 Glutaric aciduria type I – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/glutaric-aciduria-type-i/

  Undiagnosed cases typically present in the first six years of life with an acute neurological deterioration, which may be precipitated by infectious disease, vaccination or surgery. […] Patients may present in the neonatal period and infancy with nonspecific neurological symptoms, such as muscular hypotonia and delayed motor development. […] Macrocephaly is present at birth, or shortly after, in a large number (75%) of affected babies. […] If left untreated, most infants will suffer from an acute encephalopathic crisis, resulting in bilateral striatal injury with severe secondary dystonia, and occasionally subdural and retinal haemorrhage, which may be mistaken for the effects of child abuse. […] Patients with the late onset form may present with non-specific neurological symptoms, such as headaches, vertigo, and reduced fine motor skills, but do not develop striatal injury.

• #8 What is glutaric aciduria type 1?

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

  The symptoms of GA1 do not usually appear until a few months after birth. However, some babies with GA1 may be born with a larger-than-average head (macrocephaly) or muscle weakness (hypotonia). […] Within the first 3 years of life, a person with GA1 may experience an acute encephalopathic crisis. This can result in brain damage, movement problems, developmental delays, seizures, and bleeding in the brain and around the back of the eyes. Early clinical signs that may suggest acute encephalopathic crisis include: […] In other cases, symptoms may begin in adolescence or adulthood. These may include nonspecific neurological symptoms such as headaches, vertigo, and reduced fine motor skills. […] People with GA1 may also experience metabolic crisis. This occurs when compounds, such as organic acids, build up to unusually high and dangerous levels. Stressors such as illness and fasting can trigger metabolic crises.

• #9 Glutaric aciduria type 1 (GA-1)

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

  GA1 symptoms typically show up a few months after a baby is born, although some babies are born with a larger head than average. The general symptoms are: […] Poor growth […] Abnormal motor skills […] Slow development and learning difficulties […] Larger than average head at birth […] Muscle weakness (hypotonia) […] Spasms and jerking movements.

• #10 Glutaric aciduria type 1

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

  Symptoms of GA1 usually don’t appear until a few months after birth, although some babies are born with a larger-than-average head (macrocephaly). […] Children with GA1 may develop some floppiness or weakness in their muscles (hypotonia) during their first year and there’s a risk of developing bleeding around their brain (subdural haematoma). In rarer cases, bleeding can develop around the back of the eyes (retinal haemorrhage). […] Without treatment, severe and life-threatening symptoms can develop, including seizures (fits) or falling into a coma. Some children with untreated GA1 are also at risk of brain damage, which can affect muscle movement. This may lead to problems with walking, talking and swallowing. […] Children with GA1 may have episodes known as a metabolic crisis, sometimes early in their life. Symptoms of a metabolic crisis include: poor feeding or loss of appetite, lack of energy, abnormal movements, vomiting, irritability, breathing difficulties. […] You should also take your baby to hospital if they develop symptoms of a metabolic crisis, such as irritability, loss of energy or breathing difficulties.

• #11 Glutaric aciduria type I – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/glutaric-aciduria-type-i/

  Undiagnosed cases typically present in the first six years of life with an acute neurological deterioration, which may be precipitated by infectious disease, vaccination or surgery. […] Patients may present in the neonatal period and infancy with nonspecific neurological symptoms, such as muscular hypotonia and delayed motor development. […] Macrocephaly is present at birth, or shortly after, in a large number (75%) of affected babies. […] If left untreated, most infants will suffer from an acute encephalopathic crisis, resulting in bilateral striatal injury with severe secondary dystonia, and occasionally subdural and retinal haemorrhage, which may be mistaken for the effects of child abuse. […] Patients with the late onset form may present with non-specific neurological symptoms, such as headaches, vertigo, and reduced fine motor skills, but do not develop striatal injury.

• #12 Glutaric Acidemia, Type I (GA-1) – Florida Newborn Screening

  https://floridanewbornscreening.com/condition/glutaric-acidemia-type-i-ga-1/

  Glutaric acidemia, type I (GA-1) is an inherited condition in which the body is unable to break down certain proteins properly, which can lead to a harmful amount of organic acids and toxins in the body. […] A baby with GA-1 who has not been treated will start to show signs between 4 months and 2 years of age. These signs include poor appetite, sleeping longer or more often, tiredness, irritability, twitches, vomiting, weak muscle tone (hypotonia), fever, delayed growth, rigid muscles (spasticity), developmental delays, and excessive sweating. Many of these signs may occur when a baby eats foods the body cannot break down. Symptoms can be triggered by long periods of time without eating, illnesses, and infections.

• #13 Glutaric Acidemia Type 1 | Children’s Hospital Pittsburgh

  https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/glutaric-acidemia-type-1

  Children with GA-1 may have larger than average heads at birth. […] Other symptoms, such as drowsiness, muscle weakness, and poor appetite, often appear between ages 2 months and 4 years. […] The doctor will make or confirm a GA-1 diagnosis and find out how much the disease has progressed.

• #14 Glutaric Acidemia, Type I (GA-1) – Florida Newborn Screening

  https://floridanewbornscreening.com/condition/glutaric-acidemia-type-i-ga-1/

  Glutaric acidemia, type I (GA-1) is an inherited condition in which the body is unable to break down certain proteins properly, which can lead to a harmful amount of organic acids and toxins in the body. […] A baby with GA-1 who has not been treated will start to show signs between 4 months and 2 years of age. These signs include poor appetite, sleeping longer or more often, tiredness, irritability, twitches, vomiting, weak muscle tone (hypotonia), fever, delayed growth, rigid muscles (spasticity), developmental delays, and excessive sweating. Many of these signs may occur when a baby eats foods the body cannot break down. Symptoms can be triggered by long periods of time without eating, illnesses, and infections.

• #15 Glutaric aciduria type I (GA-I)

  https://healthywa.wa.gov.au/sitecore/content/Corporate/Articles/U_Z/WA-Newborn-Bloodspot-Screening-Program/Conditions-screened-for-in-WA/Glutaric-aciduria-type-I

  Vomiting […] Macrocephaly […] Encephalopathic crises […] Movement disorder, dystonia […] Seizures […] Coma and death possible.

• #16 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. […] Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria caused by glutaryl-CoA dehydrogenase (GCDH) deficiency with an estimated overall prevalence of 1 in 100,000 newborns. […] The initial progression of clinical symptoms in cases of GA-I is slow; hence GA-I is frequently left undiagnosed until an acute metabolic crisis occurs. A child suffering from GA-I usually presents with macrocephaly which is found in 75% of GA-I patients during infancy. […] Clinical presentations with acute encephalopathic crises are seen mostly between 6 and 18 months and induced by febrile illness, fasting, or immunization. Dystonia and extrapyramidal symptoms such as athetosis, seizures, and intellectual disability may be the other signs in GA-I. However some patients with GA-I remain asymptomatic, even in the adulthood. […] 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.

• #17 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. […] Patients with GA1 typically present within the first 3 years of life with acute encephalopathic crisis precipitated by catabolism. This initial crisis, or subsequent crises, can cause striatal degeneration. This striatal injury often results in motor disorder with predominantly dystonic/dyskinetic features. […] Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic hemorrhage, Chiari malformation, pituitary hormone deficiency, and epilepsy. The exact etiology of these events is unclear. […] Insidious onset GA1 describes striatal injury and motor disorder occurring without apparent crisis and is estimated to account for 20% of symptomatic presentations.

• #18 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. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] Early clinical diagnosis is hampered by the lack of characteristic or even pathognomonic signs and symptoms before an encephalopathic crisis. Macrocephaly is found in 75% of patients during infancy, but is non-specific. Therefore GA-I has been included in the disease panel of newborn screening in some countries.

• #19 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. […] The majority of untreated individuals present with a complex movement disorder (MD) with predominant dystonia mostly between the age of 3 and 36 months due to bilateral striatal damage. […] This prognostically relevant event mostly manifests acutely with an acute encephalopathic crisis, precipitated by catabolism and usually resulting in a severe MD with concomitantly increased morbidity and mortality, or insidiously without clinically apparent crisis, often resulting in a less severe MD compared with the acute manifestation. […] While the majority of NBS patients (n=195; 74.7%) remained asymptomatic, 66 of them (25.3%) developed a MD with acute (n=39), insidious (n=23) or unreported onset type (n=4).

• #20 GA-1 (glutaric acidemia type-1) – newbornscreening.info

  https://www.newbornscreening.info/ga-1-glutaric-acidemia-type-1/

  Babies with GA-1 are usually healthy at birth, although many are born with a larger than average head size. Other symptoms usually start between two months and four years of age although some people develop symptoms later. […] GA-1 causes episodes of severe illness called metabolic crises. Some of the first symptoms of a metabolic crisis are: poor appetite, extreme sleepiness or lack of energy, irritability, jitteriness, nausea, vomiting, low muscle tone (floppy muscles and joints), muscle weakness. […] If untreated, other symptoms then follow: tics or spasms of the muscles, rigid muscle contractions, called spasticity, involuntary jerking movements of the arms and legs, called dystonia, poor coordination and balance problems, increased levels of acidic substances in the blood, called metabolic acidosis, seizures, swelling of the brain or blood in the brain, coma, sometimes leading to death.

• #21 Glutaric aciduria type I – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/glutaric-aciduria-type-i/

  Undiagnosed cases typically present in the first six years of life with an acute neurological deterioration, which may be precipitated by infectious disease, vaccination or surgery. […] Patients may present in the neonatal period and infancy with nonspecific neurological symptoms, such as muscular hypotonia and delayed motor development. […] Macrocephaly is present at birth, or shortly after, in a large number (75%) of affected babies. […] If left untreated, most infants will suffer from an acute encephalopathic crisis, resulting in bilateral striatal injury with severe secondary dystonia, and occasionally subdural and retinal haemorrhage, which may be mistaken for the effects of child abuse. […] Patients with the late onset form may present with non-specific neurological symptoms, such as headaches, vertigo, and reduced fine motor skills, but do not develop striatal injury.

• #22 Glutaric aciduria type 1

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

  Symptoms of GA1 usually don’t appear until a few months after birth, although some babies are born with a larger-than-average head (macrocephaly). […] Children with GA1 may develop some floppiness or weakness in their muscles (hypotonia) during their first year and there’s a risk of developing bleeding around their brain (subdural haematoma). In rarer cases, bleeding can develop around the back of the eyes (retinal haemorrhage). […] Without treatment, severe and life-threatening symptoms can develop, including seizures (fits) or falling into a coma. Some children with untreated GA1 are also at risk of brain damage, which can affect muscle movement. This may lead to problems with walking, talking and swallowing. […] Children with GA1 may have episodes known as a metabolic crisis, sometimes early in their life. Symptoms of a metabolic crisis include: poor feeding or loss of appetite, lack of energy, abnormal movements, vomiting, irritability, breathing difficulties. […] You should also take your baby to hospital if they develop symptoms of a metabolic crisis, such as irritability, loss of energy or breathing difficulties.

• #23

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

  Glutaric aciduria type 1 (pronounced glue-ta-ric acid-ur-ee-a), or GA1, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated GA1 can cause long-term health problems, including brain damage and physical disabilities, but with newborn screening and early treatment this can be prevented. […] If your baby becomes ill, they might have an episode known as a metabolic crisis (also known as metabolic decompensation). This is caused by a rapid build-up of the harmful substances (glutaric acid and 3-hydroxyglutaric acid) in their body which can make them severely unwell. Symptoms of a metabolic crisis include: irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures, coma. […] A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening. […] 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.

• #24

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

  Glutaric aciduria type 1 (pronounced glue-ta-ric acid-ur-ee-a), or GA1, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated GA1 can cause long-term health problems, including brain damage and physical disabilities, but with newborn screening and early treatment this can be prevented. […] If your baby becomes ill, they might have an episode known as a metabolic crisis (also known as metabolic decompensation). This is caused by a rapid build-up of the harmful substances (glutaric acid and 3-hydroxyglutaric acid) in their body which can make them severely unwell. Symptoms of a metabolic crisis include: irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures, coma. […] A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening. […] 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.

• #25 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. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] Early clinical diagnosis is hampered by the lack of characteristic or even pathognomonic signs and symptoms before an encephalopathic crisis. Macrocephaly is found in 75% of patients during infancy, but is non-specific. Therefore GA-I has been included in the disease panel of newborn screening in some countries.

• #26 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. […] Patients with GA1 typically present within the first 3 years of life with acute encephalopathic crisis precipitated by catabolism. This initial crisis, or subsequent crises, can cause striatal degeneration. This striatal injury often results in motor disorder with predominantly dystonic/dyskinetic features. […] Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic hemorrhage, Chiari malformation, pituitary hormone deficiency, and epilepsy. The exact etiology of these events is unclear. […] Insidious onset GA1 describes striatal injury and motor disorder occurring without apparent crisis and is estimated to account for 20% of symptomatic presentations.

• #27

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

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. […] With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration.

• #28

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

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. […] With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration.

• #29

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

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. […] With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration.

• #30

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

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. […] With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration.

• #31 GA-1 (glutaric acidemia type-1) – newbornscreening.info

  https://www.newbornscreening.info/ga-1-glutaric-acidemia-type-1/

  Other effects of GA-1 that can happen even without a metabolic crisis are: poor growth, enlarged liver, low muscle tone, progressive spasticity, dystonia, repeated episodes of fever, excessive sweating, delays in walking and other motor skills, learning delays and intellectual disabilities, speech problems, brain damage, headaches, kidney disease. […] Even with treatment, some children continue to have episodes of metabolic crisis. This can lead to brain damage and long-term problems with involuntary movements and spasticity. After age six, metabolic crises are less common.

• #32 What is glutaric aciduria type 1?

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

  The symptoms of GA1 do not usually appear until a few months after birth. However, some babies with GA1 may be born with a larger-than-average head (macrocephaly) or muscle weakness (hypotonia). […] Within the first 3 years of life, a person with GA1 may experience an acute encephalopathic crisis. This can result in brain damage, movement problems, developmental delays, seizures, and bleeding in the brain and around the back of the eyes. Early clinical signs that may suggest acute encephalopathic crisis include: […] In other cases, symptoms may begin in adolescence or adulthood. These may include nonspecific neurological symptoms such as headaches, vertigo, and reduced fine motor skills. […] People with GA1 may also experience metabolic crisis. This occurs when compounds, such as organic acids, build up to unusually high and dangerous levels. Stressors such as illness and fasting can trigger metabolic crises.

• #33 Glutaric aciduria type 1

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

  Symptoms of GA1 usually don’t appear until a few months after birth, although some babies are born with a larger-than-average head (macrocephaly). […] Children with GA1 may develop some floppiness or weakness in their muscles (hypotonia) during their first year and there’s a risk of developing bleeding around their brain (subdural haematoma). In rarer cases, bleeding can develop around the back of the eyes (retinal haemorrhage). […] Without treatment, severe and life-threatening symptoms can develop, including seizures (fits) or falling into a coma. Some children with untreated GA1 are also at risk of brain damage, which can affect muscle movement. This may lead to problems with walking, talking and swallowing. […] Children with GA1 may have episodes known as a metabolic crisis, sometimes early in their life. Symptoms of a metabolic crisis include: poor feeding or loss of appetite, lack of energy, abnormal movements, vomiting, irritability, breathing difficulties. […] You should also take your baby to hospital if they develop symptoms of a metabolic crisis, such as irritability, loss of energy or breathing difficulties.

• #34 Glutaric aciduria type 1 – Wikipedia

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

  The severity of glutaric acidemia type 1 varies widely; some individuals are only mildly affected, while others suffer severe problems. […] Babies with glutaric acidemia type 1 often are born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. […] Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). […] Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. […] A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises, usually with following brain damage.

• #35 Glutaric aciduria type I – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/glutaric-aciduria-type-i/

  Undiagnosed cases typically present in the first six years of life with an acute neurological deterioration, which may be precipitated by infectious disease, vaccination or surgery. […] Patients may present in the neonatal period and infancy with nonspecific neurological symptoms, such as muscular hypotonia and delayed motor development. […] Macrocephaly is present at birth, or shortly after, in a large number (75%) of affected babies. […] If left untreated, most infants will suffer from an acute encephalopathic crisis, resulting in bilateral striatal injury with severe secondary dystonia, and occasionally subdural and retinal haemorrhage, which may be mistaken for the effects of child abuse. […] Patients with the late onset form may present with non-specific neurological symptoms, such as headaches, vertigo, and reduced fine motor skills, but do not develop striatal injury.

• #36 Glutaric acidemia type I: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/glutaric-acidemia-type-i/

  Glutaric acidemia type I (also called glutaric aciduria type I) is an inherited disorder in which the body is unable to process certain proteins properly. […] The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood. […] Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.

• #37 Glutaric Aciduria Type 1 (GA1) – Inherited Metabolic Disorders in Scotland

  https://www.imd.scot.nhs.uk/glutaric-aciduria-type-1-ga1/

  Babies with GA1 are at risk of developing the following symptoms: poor feeding, sleepiness, floppiness, abnormal movements, vomiting, breathing difficulties and fast breathing, coldness. […] These symptoms can be controlled with treatment. Left untreated, GA1 can cause long-term damage to the brain, affecting muscle movement and the ability to sit, walk, talk or swallow. […] When babies with GA1 become ill, they might show symptoms of metabolic crisis. A metabolic crisis is a period of time when the effects of the condition make your child seriously ill. […] Some children with GA1 have been known to bleed around their brain (subdural haemorrhage). In rare cases they can develop bleeds in the back of the eyes (retinal haemorrhages).

• #38 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. […] Patients with GA1 typically present within the first 3 years of life with acute encephalopathic crisis precipitated by catabolism. This initial crisis, or subsequent crises, can cause striatal degeneration. This striatal injury often results in motor disorder with predominantly dystonic/dyskinetic features. […] Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic hemorrhage, Chiari malformation, pituitary hormone deficiency, and epilepsy. The exact etiology of these events is unclear. […] Insidious onset GA1 describes striatal injury and motor disorder occurring without apparent crisis and is estimated to account for 20% of symptomatic presentations.

• #39 Orphanet: Glutaryl-CoA dehydrogenase deficiency

  https://www.orpha.net/en/disease/detail/25

  Neonates are mainly asymptomatic, although 75 % present with macrocephaly and possibly show hypotonia and irritability. […] If undiagnosed, the initial acute encephalopathic crisis occurs between 3-36 months, typically precipitated by an intercurrent febrile illness, vaccination or a surgical intervention, and characterized by hypotonia, loss of motor skills and convulsions resulting in bilateral striatal injury with severe secondary dystonia and occasionally subdural and retinal hemorrhage. […] With age (6 years) and with appropriate treatment, the risk of encephalopathic crises subsides. […] In some patients, hypotonia and dystonia develop gradually with no encephalopathic crisis, which is known as late-onset or insidious-onset GDD.

• #40 Glutaric aciduria type 1 | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/glutaric-aciduria-type-1?lang=us

  Presentation is variable, but typically affected neonates develop macrocephaly in the first few months of life, but are otherwise asymptomatic. […] Most present with acute encephalopathy following infection or acute catabolic state e.g. gastrointestinal disturbance. The initial presentation may therefore resemble viral encephalitis or acute disseminated encephalomyelitis (ADEM). Following the acute presentation; extrapyramidal symptoms develop which correlate on imaging with striatal involvement and subsequent necrosis. […] Some patients present with an insidious onset without episodes of acute deterioration, and others present as adults with progressive encephalopathy, or are asymptomatic. […] Glutaric aciduria type 1 is a slowly progressive disease, with episodes of acute deterioration, often following infection. The progressive extrapyramidal symptoms are disabling, but mental capabilities may remain preserved. If untreated, death is usually in the first decade, in the setting of an acute exacerbation.

• #41 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. Here we presented a 3-year-old girl with hypotonia and dystonia diagnosed with GA-I although the repeated analysis of the carnitine profile and organic acid analyses were normal. The patient has motor, mental retardation, hypotonia. Her weight standard deviation score (SDS) was -1.86 SDS, height SDS was -0.55 SDS, head circumference SDS was -1.01. Dystonia and spastic tetraparesis developed on her follow-up. Cranial magnetic resonance imaging revealed bilateral cortical atrophy and bilateral striatal and caudate nucleus T2 flair hyperintensities. Acute neurological deterioration occurs most frequently between 6 and 18 months usually triggered by febrile illnesses or immunization. Movement disorder, dystonia, seizures and extrapyramidal symptoms are presented. In few patients, neurological disease has been demonstrated in the absence of any encephalopathic crisis termed as insidious-onset type and late onset type. Here we presented a 4-year-old girl with hypotonia and dystonia and diagnosed with GA-I although the repeated analysis of the carnitine profile and organic acid analyses were normal. On physical examination severe hypotonia, and dystonia were detected, deep brain tendon reflexes were increased, and other systems were normal. Feeding difficulties, hyper salivation and spastic tetra paresis developed on her follow-up. During follow up clinical progression was observed and control cranial MRI investigation was performed. Findings were similar when compared with previous cranial MR. In our patient there was no history of acute encephalopathic crisis, but progressive neurodegeneration was detected. Like to the literature dystonia was the dominant extrapyramidal symptom in our patient. Urine organic acid analysis usually shows increased levels of GA, 3-OH-GA, glutaryl-CoA, glutarylcarnitine although GA and dicarboxylic carnitines can be completely normal in some patients. The MRI findings of our patient such as striatal hyperintensities and temporal atrophy are common in GA-I patients. During follow up, spot blood free carnitine levels of the patient were normal. Also, repeated urine organic acid analyses were all normal. With the basic metabolic treatment, we didn’t detect progression of the patients symptoms but also no beneficial effect. GA-I is a treatable inborn metabolic disorder. It is important including GA-I in the differential diagnosis of leukoencephalopathy, dystonia combined with macrocephaly or not. The encephalopathic crisis may be absent and glutaryl carnitine elevation and urine glutaric acid elevation can not be detected.

• #42 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Late-onset GA1 refers to diagnosis any time after 6 years of life. Reported patients are exclusively high excretors and symptoms may be nonspecific, including headache, memory loss, dysarthria, weakness, epilepsy, and difficulty with coordination. […] Among this cohort of patients attending our National Centre, distinctive clinical events occurring after 6 years of age were also observed, details of which are supplied, although the exact etiology of these phenomena is uncertain. […] We continue to show the positive effect early diagnosis and treatment, through high-risk screening, has on reduction of manifestations of GA1 such as reduction in motor disorder at school age and improved attendance at mainstream school.

• #43 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Late-onset GA1 refers to diagnosis any time after 6 years of life. Reported patients are exclusively high excretors and symptoms may be nonspecific, including headache, memory loss, dysarthria, weakness, epilepsy, and difficulty with coordination. […] Among this cohort of patients attending our National Centre, distinctive clinical events occurring after 6 years of age were also observed, details of which are supplied, although the exact etiology of these phenomena is uncertain. […] We continue to show the positive effect early diagnosis and treatment, through high-risk screening, has on reduction of manifestations of GA1 such as reduction in motor disorder at school age and improved attendance at mainstream school.

• #44 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, 80-90% 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. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. […] Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. […] While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease.

• #45 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, 80-90% 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. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. […] Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. […] While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease.

• #46

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

  Hoffmann et al. (1995) presented the clinical findings in more than 21 patients with GCDH deficiency. […] Merinero et al. (1995) described 7 new patients with severe deficiency of glutaryl-CoA dehydrogenase in cultured skin fibroblasts, only 3 of which excreted high levels of glutaric acid in the urine. […] Bjugstad et al. (2000) performed a forward, stepwise, multiple regression analysis to find predictors for outcome in 115 previously described patients with glutaric acidemia I. […] Strauss et al. (2003) summarized the clinical characteristics of 37 Amish and 40 non-Amish patients with GA I. […] Bahr et al. (2002) reported a previously healthy 19-year-old woman who presented with recurrent headaches, oculomotor symptoms, and a severe leukoencephalopathy on MRI. […] Kulkens et al. (2005) reported 2 unrelated patients who developed neurologic signs at ages 35 and 15 years, respectively.

• #47 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, 80-90% 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. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. […] Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. […] While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease.

• #48

  https://journals.lww.com/neur/fulltext/2024/11000/a_rare_presentation_of_glutaric_aciduria_type_1_in.32.aspx

  The MRI findings were pivotal in raising the suspicion of GA1 as white matter changes are common in late-onset GA1 patients. MRI shows white matter signal abnormalities involving the deep frontoparietal white matter seem more frequent in adults and increase with age. Some may also have subependymal nodules localized at the roof and medial walls of the lateral ventricles, representing another useful neuroimaging marker.

• #49 Glutaric acidemia type I: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/glutaric-acidemia-type-i/

  Glutaric acidemia type I (also called glutaric aciduria type I) is an inherited disorder in which the body is unable to process certain proteins properly. […] The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood. […] Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.

• #50 Glutaric acidemia, type I (GA-I) | New York State Department of Health, Wadsworth Center

  https://www.wadsworth.org/public-health-programs/newborn-screening/newborn-screening-program/glutaric-acidemia-type-i-ga-i

  Newborns with GA-I may not have obvious symptoms at birth, aside from large head size (macrocephaly). Untreated, symptoms may include poor growth and episodes of dystonia and athetosis (unusual movements of the limbs), rigidness and spasticity. The episodes are usually triggered by an illness. […] Outcome is variable, and dependent on multiple factors, including the severity of disease and response to treatments.

• #51 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, 80-90% 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. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. […] Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. […] While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease.

• #52 Glutaric acidemia, GCDH-related | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/glutaric-acidemia-gcdh-related/

  Children who have already had a metabolic crisis are likely to develop permanent brain damage that causes severe motor difficulties and involuntary spastic movement. The disease can be fatal in children who go untreated during a metabolic crisis. The 20-year survival rate in children with severe motor and other disabilities is 50%.

• #53 Glutaric aciduria type 1 | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/glutaric-aciduria-type-1?lang=us

  Presentation is variable, but typically affected neonates develop macrocephaly in the first few months of life, but are otherwise asymptomatic. […] Most present with acute encephalopathy following infection or acute catabolic state e.g. gastrointestinal disturbance. The initial presentation may therefore resemble viral encephalitis or acute disseminated encephalomyelitis (ADEM). Following the acute presentation; extrapyramidal symptoms develop which correlate on imaging with striatal involvement and subsequent necrosis. […] Some patients present with an insidious onset without episodes of acute deterioration, and others present as adults with progressive encephalopathy, or are asymptomatic. […] Glutaric aciduria type 1 is a slowly progressive disease, with episodes of acute deterioration, often following infection. The progressive extrapyramidal symptoms are disabling, but mental capabilities may remain preserved. If untreated, death is usually in the first decade, in the setting of an acute exacerbation.

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

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

  The basal ganglia in the brain controls movement. The build-up of glutaric acid damages the basal ganglia and causes movement problems. […] A metabolic crisis can trigger the movement problems. This is because there is a build-up of glutaric acid and other toxic chemicals. It is usually caused by childhood infections or viruses causing high temperatures, vomiting and diarrhoea. Avoidance of a metabolic crisis is essential. […] Babies with GA1 are usually healthy at birth although many are born with a larger than average head size. […] GA1 is a serious inherited metabolic disorder that can lead to severe movement problems. Children are very vulnerable in the first 6 years of life. Damage can be prevented with a protein-restricted diet, a protein substitute and carnitine. […] With good management, severe movement problems can be prevented in the majority of children.

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

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

  The basal ganglia in the brain controls movement. The build-up of glutaric acid damages the basal ganglia and causes movement problems. […] A metabolic crisis can trigger the movement problems. This is because there is a build-up of glutaric acid and other toxic chemicals. It is usually caused by childhood infections or viruses causing high temperatures, vomiting and diarrhoea. Avoidance of a metabolic crisis is essential. […] Babies with GA1 are usually healthy at birth although many are born with a larger than average head size. […] GA1 is a serious inherited metabolic disorder that can lead to severe movement problems. Children are very vulnerable in the first 6 years of life. Damage can be prevented with a protein-restricted diet, a protein substitute and carnitine. […] With good management, severe movement problems can be prevented in the majority of children.

• #56 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201014/Study-summarizes-treatment-and-management-of-glutaric-acidemia-type-1.aspx

  Before the CSC’s founding in 1989, 90% of infants and young children with GA1 suffered a catastrophic form of acute neurological degeneration. The brain injury of GA1 leaves children mute, wheelchair-dependent, and fully disabled by generalized dystonia, and often results in complications such as scoliosis, hip dislocation, pulmonary aspiration, chronic pain, and untimely death. […] Today, with the benefit of early diagnosis, dietary therapy, and an effective hospital protocol, only 7% of children born with GA1 suffer brain injury. Specifically, state newborn screening coupled with strict dietary management reduces the risk of brain injury 14-fold, and uninjured children with GA1 have normal growth, motor development, and cognitive function. […] Overall, early diagnosis of GA1 with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective – preventing over 90% of brain injuries. The need for dietary and emergency IV therapies beyond early childhood is uncertain at this time.

• #57 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. […] The majority of untreated individuals present with a complex movement disorder (MD) with predominant dystonia mostly between the age of 3 and 36 months due to bilateral striatal damage. […] This prognostically relevant event mostly manifests acutely with an acute encephalopathic crisis, precipitated by catabolism and usually resulting in a severe MD with concomitantly increased morbidity and mortality, or insidiously without clinically apparent crisis, often resulting in a less severe MD compared with the acute manifestation. […] While the majority of NBS patients (n=195; 74.7%) remained asymptomatic, 66 of them (25.3%) developed a MD with acute (n=39), insidious (n=23) or unreported onset type (n=4).

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

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

  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. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration. […] The major neurological complications in GA-I are the manifestation of a complex movement disorder and subdural hemorrhage.

• #59

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

  Glutaric aciduria type 1 (pronounced glue-ta-ric acid-ur-ee-a), or GA1, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated GA1 can cause long-term health problems, including brain damage and physical disabilities, but with newborn screening and early treatment this can be prevented. […] If your baby becomes ill, they might have an episode known as a metabolic crisis (also known as metabolic decompensation). This is caused by a rapid build-up of the harmful substances (glutaric acid and 3-hydroxyglutaric acid) in their body which can make them severely unwell. Symptoms of a metabolic crisis include: irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures, coma. […] A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening. […] 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.

• #60 Orphanet: Glutaryl-CoA dehydrogenase deficiency

  https://www.orpha.net/en/disease/detail/25

  Neonates are mainly asymptomatic, although 75 % present with macrocephaly and possibly show hypotonia and irritability. […] If undiagnosed, the initial acute encephalopathic crisis occurs between 3-36 months, typically precipitated by an intercurrent febrile illness, vaccination or a surgical intervention, and characterized by hypotonia, loss of motor skills and convulsions resulting in bilateral striatal injury with severe secondary dystonia and occasionally subdural and retinal hemorrhage. […] With age (6 years) and with appropriate treatment, the risk of encephalopathic crises subsides. […] In some patients, hypotonia and dystonia develop gradually with no encephalopathic crisis, which is known as late-onset or insidious-onset GDD.

• #61 GA-1 (glutaric acidemia type-1) – newbornscreening.info

  https://www.newbornscreening.info/ga-1-glutaric-acidemia-type-1/

  Other effects of GA-1 that can happen even without a metabolic crisis are: poor growth, enlarged liver, low muscle tone, progressive spasticity, dystonia, repeated episodes of fever, excessive sweating, delays in walking and other motor skills, learning delays and intellectual disabilities, speech problems, brain damage, headaches, kidney disease. […] Even with treatment, some children continue to have episodes of metabolic crisis. This can lead to brain damage and long-term problems with involuntary movements and spasticity. After age six, metabolic crises are less common.

• #62 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. […] Patients with GA1 typically present within the first 3 years of life with acute encephalopathic crisis precipitated by catabolism. This initial crisis, or subsequent crises, can cause striatal degeneration. This striatal injury often results in motor disorder with predominantly dystonic/dyskinetic features. […] Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic hemorrhage, Chiari malformation, pituitary hormone deficiency, and epilepsy. The exact etiology of these events is unclear. […] Insidious onset GA1 describes striatal injury and motor disorder occurring without apparent crisis and is estimated to account for 20% of symptomatic presentations.

• #63 Glutaric aciduria | MedLink Neurology

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

  In a dystonic child with glutaric aciduria type I striatal injury becomes evident on brain MRI scans spreading in a dorsoventral direction, with the extent of the putaminal lesion predicting the severity of the movement disorder. […] Regardless of acute and insidious onset, motor dysfunction due to striatal injury is the most important and prognostically relevant complication, whereas cognitive functions have been thought to be mostly preserved. However, cognitive deficits may occur and are more frequently found in the high-excreter group of patients despite early diagnosis and treatment. […] 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. Deviations from emergency treatment increase the risk of acute-onset dystonia, whereas nonadherence to dietary treatment is associated with insidious-onset dystonia. Regardless of therapy, however, kidney function tends to decline with age, starting in adolescence or adulthood. White matter abnormalities progress with age in individuals with the biochemical high-excreter phenotype who also demonstrated lower cognitive performance compared to low excretors.

• #64 Audiological and otologic manifestations of glutaric aciduria type I | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-020-01571-w

  Hearing loss was found in 76.9% (10/13) of GA-1 patients, including slight hearing loss in 46.1% (6/13) of patients, mild hearing loss in 15.4% (2/13) of patients, and moderate hearing loss in 7.7% (1/13) of patients. […] A high prevalence of hearing impairment is found in GA-1 patients. […] Most children are found to have some degree of speech difficulty (e.g., dysarthria, articulation difficulties). […] We found that a high percent of patients with GA-1 encountered slight to moderate sensorineural hearing loss in this study. […] We found that 75% of GA-1 patients had varying degrees of hearing loss in our study. […] In our study, hearing loss was found in 69.2% of patients, which is much higher than the global prevalence of pediatric hearing impairment. […] Hearing loss is a common issue in patients with GA-1. Clinicians should consider the high prevalence of hearing loss in these patients, especially in patients with encephalopathic crisis or ICU admittance.

• #65 Audiological and otologic manifestations of glutaric aciduria type I | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-020-01571-w

  Hearing loss was found in 76.9% (10/13) of GA-1 patients, including slight hearing loss in 46.1% (6/13) of patients, mild hearing loss in 15.4% (2/13) of patients, and moderate hearing loss in 7.7% (1/13) of patients. […] A high prevalence of hearing impairment is found in GA-1 patients. […] Most children are found to have some degree of speech difficulty (e.g., dysarthria, articulation difficulties). […] We found that a high percent of patients with GA-1 encountered slight to moderate sensorineural hearing loss in this study. […] We found that 75% of GA-1 patients had varying degrees of hearing loss in our study. […] In our study, hearing loss was found in 69.2% of patients, which is much higher than the global prevalence of pediatric hearing impairment. […] Hearing loss is a common issue in patients with GA-1. Clinicians should consider the high prevalence of hearing loss in these patients, especially in patients with encephalopathic crisis or ICU admittance.

• #66 Glutaric aciduria | MedLink Neurology

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

  In a dystonic child with glutaric aciduria type I striatal injury becomes evident on brain MRI scans spreading in a dorsoventral direction, with the extent of the putaminal lesion predicting the severity of the movement disorder. […] Regardless of acute and insidious onset, motor dysfunction due to striatal injury is the most important and prognostically relevant complication, whereas cognitive functions have been thought to be mostly preserved. However, cognitive deficits may occur and are more frequently found in the high-excreter group of patients despite early diagnosis and treatment. […] 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. Deviations from emergency treatment increase the risk of acute-onset dystonia, whereas nonadherence to dietary treatment is associated with insidious-onset dystonia. Regardless of therapy, however, kidney function tends to decline with age, starting in adolescence or adulthood. White matter abnormalities progress with age in individuals with the biochemical high-excreter phenotype who also demonstrated lower cognitive performance compared to low excretors.

• #67 Glutaric aciduria | MedLink Neurology

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

  In a dystonic child with glutaric aciduria type I striatal injury becomes evident on brain MRI scans spreading in a dorsoventral direction, with the extent of the putaminal lesion predicting the severity of the movement disorder. […] Regardless of acute and insidious onset, motor dysfunction due to striatal injury is the most important and prognostically relevant complication, whereas cognitive functions have been thought to be mostly preserved. However, cognitive deficits may occur and are more frequently found in the high-excreter group of patients despite early diagnosis and treatment. […] 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. Deviations from emergency treatment increase the risk of acute-onset dystonia, whereas nonadherence to dietary treatment is associated with insidious-onset dystonia. Regardless of therapy, however, kidney function tends to decline with age, starting in adolescence or adulthood. White matter abnormalities progress with age in individuals with the biochemical high-excreter phenotype who also demonstrated lower cognitive performance compared to low excretors.

• #68 Glutaric aciduria type 1: Diagnosis, clinical features and long‐term outcome in a large cohort of 34 Irish patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9259398/

  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. […] Patients with GA1 typically present within the first 3 years of life with acute encephalopathic crisis precipitated by catabolism. This initial crisis, or subsequent crises, can cause striatal degeneration. This striatal injury often results in motor disorder with predominantly dystonic/dyskinetic features. […] Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic hemorrhage, Chiari malformation, pituitary hormone deficiency, and epilepsy. The exact etiology of these events is unclear. […] Insidious onset GA1 describes striatal injury and motor disorder occurring without apparent crisis and is estimated to account for 20% of symptomatic presentations.

• #69 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

  In contrast, most TMS patients (349/386; 90.4%) were symptomatic at time of diagnosis and had a MD with acute (244/349; 69.9%), insidious (79/349; 22.6%), or unreported onset type (26/349; 7.5%). […] Motor development was delayed in the vast majority of this group (285/349; 81.7%), and 63 (18.1%) symptomatic patients of the TMS group died during the reported study interval. […] 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. […] 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.

• #70 Glutaric aciduria | MedLink Neurology

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

  In a dystonic child with glutaric aciduria type I striatal injury becomes evident on brain MRI scans spreading in a dorsoventral direction, with the extent of the putaminal lesion predicting the severity of the movement disorder. […] Regardless of acute and insidious onset, motor dysfunction due to striatal injury is the most important and prognostically relevant complication, whereas cognitive functions have been thought to be mostly preserved. However, cognitive deficits may occur and are more frequently found in the high-excreter group of patients despite early diagnosis and treatment. […] 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. Deviations from emergency treatment increase the risk of acute-onset dystonia, whereas nonadherence to dietary treatment is associated with insidious-onset dystonia. Regardless of therapy, however, kidney function tends to decline with age, starting in adolescence or adulthood. White matter abnormalities progress with age in individuals with the biochemical high-excreter phenotype who also demonstrated lower cognitive performance compared to low excretors.

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

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

  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. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration. […] The major neurological complications in GA-I are the manifestation of a complex movement disorder and subdural hemorrhage.

• #72

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

  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. […] The characteristic neurological sequela of these crises is acute bilateral striatal injury and, subsequently, a complex movement disorder. Dystonia is the dominant extrapyramidal symptom, usually superimposed on axial hypotonia. […] With aging, there is a tendency for a fixed dystonia and akinetic-rigid parkinsonism to develop. Morbidity and mortality is high in patients who have had a crisis. […] In contrast to patients identified presymptomatically, outcome in GA-I is poor when diagnosed after the manifestation of neurological disease. The value of metabolic treatment is unclear in patients with severe neurological symptoms, but individual patients may benefit by prevention of progressive neurological deterioration.

• #73 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

  In contrast, most TMS patients (349/386; 90.4%) were symptomatic at time of diagnosis and had a MD with acute (244/349; 69.9%), insidious (79/349; 22.6%), or unreported onset type (26/349; 7.5%). […] Motor development was delayed in the vast majority of this group (285/349; 81.7%), and 63 (18.1%) symptomatic patients of the TMS group died during the reported study interval. […] 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. […] 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.

• #74 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

  Differences between late-onset patients and early treated control patients most likely reflect greater cumulative neurotoxicity in individuals remaining undiagnosed and untreated for years, even decades as well as the higher long-term risk of high excretors for intracerebral accumulation of neurotoxic metabolites compared to low excretors.

• #75 Glutaric aciduria | MedLink Neurology

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

  In a dystonic child with glutaric aciduria type I striatal injury becomes evident on brain MRI scans spreading in a dorsoventral direction, with the extent of the putaminal lesion predicting the severity of the movement disorder. […] Regardless of acute and insidious onset, motor dysfunction due to striatal injury is the most important and prognostically relevant complication, whereas cognitive functions have been thought to be mostly preserved. However, cognitive deficits may occur and are more frequently found in the high-excreter group of patients despite early diagnosis and treatment. […] 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. Deviations from emergency treatment increase the risk of acute-onset dystonia, whereas nonadherence to dietary treatment is associated with insidious-onset dystonia. Regardless of therapy, however, kidney function tends to decline with age, starting in adolescence or adulthood. White matter abnormalities progress with age in individuals with the biochemical high-excreter phenotype who also demonstrated lower cognitive performance compared to low excretors.

• #76 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. […] The majority of untreated individuals present with a complex movement disorder (MD) with predominant dystonia mostly between the age of 3 and 36 months due to bilateral striatal damage. […] This prognostically relevant event mostly manifests acutely with an acute encephalopathic crisis, precipitated by catabolism and usually resulting in a severe MD with concomitantly increased morbidity and mortality, or insidiously without clinically apparent crisis, often resulting in a less severe MD compared with the acute manifestation. […] While the majority of NBS patients (n=195; 74.7%) remained asymptomatic, 66 of them (25.3%) developed a MD with acute (n=39), insidious (n=23) or unreported onset type (n=4).

• #77 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

  In contrast, most TMS patients (349/386; 90.4%) were symptomatic at time of diagnosis and had a MD with acute (244/349; 69.9%), insidious (79/349; 22.6%), or unreported onset type (26/349; 7.5%). […] Motor development was delayed in the vast majority of this group (285/349; 81.7%), and 63 (18.1%) symptomatic patients of the TMS group died during the reported study interval. […] 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. […] 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.

• #78

  https://www.koreascience.kr/article/JAKO202118350320355.page

  Glutaric aciduria type 1 (GA1; OMIM #231670) is a rare autosomal recessive-inherited neurometabolic disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH), which is encoded by the GCDH gene. […] The treatments of GA1 known to date are metabolic maintenance treatment based on a low-lysine diet and emergency treatment during acute illness. However, treatment after the onset of neurological symptoms has limited effectiveness and is associated with poor outcomes, and the effect of treatment and disease course after treatment are not good. […] After the implementation of newborn screening, the incidence of acute encephalopathic crisis fell to 10%-20% with early diagnosis, preventative dietary management, and aggressive medical intervention during acute episodes. […] Recently, several cohort studies have been published on the natural course and treatment of GA1 patients. This mini review will cover the clinical symptoms, natural history, and treatment of GA1 through a literature review.

• #79 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201014/Study-summarizes-treatment-and-management-of-glutaric-acidemia-type-1.aspx

  Before the CSC’s founding in 1989, 90% of infants and young children with GA1 suffered a catastrophic form of acute neurological degeneration. The brain injury of GA1 leaves children mute, wheelchair-dependent, and fully disabled by generalized dystonia, and often results in complications such as scoliosis, hip dislocation, pulmonary aspiration, chronic pain, and untimely death. […] Today, with the benefit of early diagnosis, dietary therapy, and an effective hospital protocol, only 7% of children born with GA1 suffer brain injury. Specifically, state newborn screening coupled with strict dietary management reduces the risk of brain injury 14-fold, and uninjured children with GA1 have normal growth, motor development, and cognitive function. […] Overall, early diagnosis of GA1 with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective – preventing over 90% of brain injuries. The need for dietary and emergency IV therapies beyond early childhood is uncertain at this time.

• #80

  https://www.koreascience.kr/article/JAKO202118350320355.page

  Glutaric aciduria type 1 (GA1; OMIM #231670) is a rare autosomal recessive-inherited neurometabolic disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH), which is encoded by the GCDH gene. […] The treatments of GA1 known to date are metabolic maintenance treatment based on a low-lysine diet and emergency treatment during acute illness. However, treatment after the onset of neurological symptoms has limited effectiveness and is associated with poor outcomes, and the effect of treatment and disease course after treatment are not good. […] After the implementation of newborn screening, the incidence of acute encephalopathic crisis fell to 10%-20% with early diagnosis, preventative dietary management, and aggressive medical intervention during acute episodes. […] Recently, several cohort studies have been published on the natural course and treatment of GA1 patients. This mini review will cover the clinical symptoms, natural history, and treatment of GA1 through a literature review.

• #81 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201014/Study-summarizes-treatment-and-management-of-glutaric-acidemia-type-1.aspx

  Before the CSC’s founding in 1989, 90% of infants and young children with GA1 suffered a catastrophic form of acute neurological degeneration. The brain injury of GA1 leaves children mute, wheelchair-dependent, and fully disabled by generalized dystonia, and often results in complications such as scoliosis, hip dislocation, pulmonary aspiration, chronic pain, and untimely death. […] Today, with the benefit of early diagnosis, dietary therapy, and an effective hospital protocol, only 7% of children born with GA1 suffer brain injury. Specifically, state newborn screening coupled with strict dietary management reduces the risk of brain injury 14-fold, and uninjured children with GA1 have normal growth, motor development, and cognitive function. […] Overall, early diagnosis of GA1 with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective – preventing over 90% of brain injuries. The need for dietary and emergency IV therapies beyond early childhood is uncertain at this time.

• #82 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

  In contrast, most TMS patients (349/386; 90.4%) were symptomatic at time of diagnosis and had a MD with acute (244/349; 69.9%), insidious (79/349; 22.6%), or unreported onset type (26/349; 7.5%). […] Motor development was delayed in the vast majority of this group (285/349; 81.7%), and 63 (18.1%) symptomatic patients of the TMS group died during the reported study interval. […] 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. […] 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.

• #83 A Case of Mistaken Identity: Glutaric Aciduria Type I Masquerading as Postmeningitic Hydrocephalus – Journal of Clinical Imaging Science

  https://clinicalimagingscience.org/a-case-of-mistaken-identity-glutaric-aciduria-type-i-masquerading-as-postmeningitic-hydrocephalus/

  Early diagnosis and early therapy reduce the risk of acute dystonia and prevent the progression of the neurological disabilities. […] The radiologist therefore has a critical role in the early imaging diagnosis of this condition as early institution of therapy can halt the progression of the disease. Any diagnostic delay, whether clinical or imaging, leads to progressive and irreversible neurological damage. […] Therefore, an astute radiologist plays a vital role in arriving at an early diagnosis of GAT 1, for timely institution of therapy, which can delay the progressive neurological deterioration.

• #84 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20201014/Study-summarizes-treatment-and-management-of-glutaric-acidemia-type-1.aspx

  Before the CSC’s founding in 1989, 90% of infants and young children with GA1 suffered a catastrophic form of acute neurological degeneration. The brain injury of GA1 leaves children mute, wheelchair-dependent, and fully disabled by generalized dystonia, and often results in complications such as scoliosis, hip dislocation, pulmonary aspiration, chronic pain, and untimely death. […] Today, with the benefit of early diagnosis, dietary therapy, and an effective hospital protocol, only 7% of children born with GA1 suffer brain injury. Specifically, state newborn screening coupled with strict dietary management reduces the risk of brain injury 14-fold, and uninjured children with GA1 have normal growth, motor development, and cognitive function. […] Overall, early diagnosis of GA1 with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective – preventing over 90% of brain injuries. The need for dietary and emergency IV therapies beyond early childhood is uncertain at this time.

• #85 A Case of Mistaken Identity: Glutaric Aciduria Type I Masquerading as Postmeningitic Hydrocephalus – Journal of Clinical Imaging Science

  https://clinicalimagingscience.org/a-case-of-mistaken-identity-glutaric-aciduria-type-i-masquerading-as-postmeningitic-hydrocephalus/

  Early diagnosis and early therapy reduce the risk of acute dystonia and prevent the progression of the neurological disabilities. […] The radiologist therefore has a critical role in the early imaging diagnosis of this condition as early institution of therapy can halt the progression of the disease. Any diagnostic delay, whether clinical or imaging, leads to progressive and irreversible neurological damage. […] Therefore, an astute radiologist plays a vital role in arriving at an early diagnosis of GAT 1, for timely institution of therapy, which can delay the progressive neurological deterioration.

• #86 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

  In contrast, most TMS patients (349/386; 90.4%) were symptomatic at time of diagnosis and had a MD with acute (244/349; 69.9%), insidious (79/349; 22.6%), or unreported onset type (26/349; 7.5%). […] Motor development was delayed in the vast majority of this group (285/349; 81.7%), and 63 (18.1%) symptomatic patients of the TMS group died during the reported study interval. […] 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. […] 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.

• #87 Glutaric aciduria type 1 | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/glutaric-aciduria-type-1?lang=us

  Early post-natal diagnosis should be sought as an early treatment prior to metabolic decompensation has the best chance of preventing neurological deterioration. For this reason, all siblings of an affected child and all future pregnancies should be screened for the disease. Nevertheless, some cases are progressive despite all appropriate treatment.

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