Glutaric aciduria type 1 is a rare neurometabolic disease with high morbidity. Glutaric acidemia type 1 glutarylcoa dehydrogenase deficiency the british inherited metabolic disease group bimdg has published on its website guidelines for the emergency management of patients with inhereited metabolic disorders. Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. Add prescribed amount of glutarex1 powder and other ingredients if recommended. Ct and mr of the brain in glutaric acidemia type i.
Ga1 has an estimated overall prevalence of 1 in 100,000. Glutaric aciduria and suspected child abuse archives of. Glutaric acidemia type 1 is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Glutaric aciduria type 1 is caused by a defect in the gene that codes for glutarylcoa dehydrogenase gcdh, which catalyzes the formation of crotonylcoa from glutarylcoa fig. Glutaric aciduria type 1 radiology reference article. Glutaric aciduria type i nord national organization for. Glutaric acidemia type 1 or glutaric aciduria, ga1, or gat1 is an inherited disorder in which the body is unable to breakdown completely the amino acids lysine, hydroxylysine and tryptophan. Glutaric aciduria type ii nord national organization. Excessive levels of their intermediate breakdown products glutaric acid, glutarylcoa, 3hydroxyglutaric acid, glutaconic acid can accumulate and cause damage to the brain and also other organs. Disease bioinformatics research of glutaric aciduria, type 1 has been linked to inborn errors of metabolism, acidemia, dystonia disorders, atrophy, macrocephaly. Affected patients can present with brain atrophy and macrocephaly and with acute dystonia secondary to striatal degeneration in most cases triggered by an.
Subdural haematomas have been found in symptomatic and asymptomatic patients, even in the immediate postnatal period. The course on glutaric aciduria type 1 includes information on diseasespecific biochemistry, nutrition management and monitoring. This is where the individual is unable to breakdown certain proteins and the result is a build up of chemicals, usually acids in the body. Coa dehydrogenase deficiency and is a cause of acute striatal necrosis in infancy. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills psychomotor delay, speech delay, involuntary muscle cramping dystonia, and spasms and weakness of the arms and legs spastic quadriparesis. Glutaric aciduria type 1 importance of early diagnosis. Glutaric aciduria type 1 ga1 is a rare but serious inherited condition.
Protein from foods gcdhgcgcddh what is glutaric aciduria. Clinical experience teaches us two things about ga1. Boy n, mengler k, thimm e, et al newborn screening. Of note, the ga 1 phenotype can vary widely between untreated family members with the same genotype, primarily as a function of the age at which the first acute encephalopathic crisis occurred. The mutations result in deficient or complete absence of activity of multiple acylcoa dehydrogenase madd enzymes needed to break down fats and proteins that the body uses for energy. Glutaric acidemia type 1 is also known as glutaric aciduria. At present, the treatment for ga1 involves a protein restricted diet for life and taking regular dietary.
It means the body cant process certain amino acids, causing a harmful buildup of substances in the blood and urine. Excessive levels of their intermediate breakdown products glutaric acid, glutarylcoa, 3hydroxyglutaric acid, glutaconic acid can accumulate and cause damage to the brain and also other organs, but particularly the basal ganglia, which. Subdural hemorrhage as an initial sign of glutaric aciduria type 1. Mutations in the gcdh gene cause glutaric aciduria, type 1. Without enough of the enzyme, the breakdown products of these amino acids build up in tissues of the body.
Glutaric aciduria type 1 ga1 is an autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by deficiency of glutarylcoa dehydrogenase. Pour mixture into clean feeding bottles or container. Glutaric acidauri, type 1 occurs in greater than1 in 75,000 caucasian live births. The case was initially interpreted as adem versus viral encephalitis which may simulate glutaric aciduria in presentation. Case report singapore med j 2010, 514 e69 mr imaging findings of glutaric aciduria type ii mumtaz h a, gupta v, singh p, marwaha r k, khandelwal n abstract glutaric aciduria type ii, also known as multiple acyl coenzyme a dehydrogenase deficiency, is an autosomal recessive, mitochondria. Glutarex 1 amino acidmodified infant formula with iron. Glutaric aciduria type i synonym, glutaric acidemia type i is a rare organic aciduria. Glutaric aciduria type 1 in south africahigh incidence of glutarylcoa dehydrogenase deficiency in black south africans. The study of glutaric aciduria, type 1 has been mentioned in research publications which can be found using our bioinformatics tool below. The phenotypic spectrum of untreated glutaric acidemia type 1 ga 1 ranges from the more common form infantileonset disease to the less common form lateronset disease i. Dietary management aims to prevent the accumulation of lysine and tryptophan by means of a lowprotein diet and supplementing the. Normally, our bodies break down protein foods like meat and fish into amino acids.
Here are the ones for the management of an acute decompensation in children and adults with a type 1 glutaric. Glutaric acidemia type i genetics home reference nih. The respective amounts of these substances result in an oaorotidine ratio of above 10. Glutaric acidemia type i ga1 is a genetic metabolic disorder. Imaging, therefore, has an important role to play as the mri features can be characteristic. To describe the mr imaging abnormalities in glutaric aciduria type 1 and to identify any association between the clinical and imaging features. External links yamaguchi s ryoikibetsu shokogun shirizu 01 jan 2003. A correct and timely diagnosis of oa1 is key to effective treatment for the condition. Bennett mj, marlow n, pollitt rj, wales jkh 1986 glutaric aciduria type 1. Glutaric aciduria type 1 ga1 the building blocks of protein are called amino acids. Overview in glutaric acidemia type 1 ga1, defective activity of glutarylcoa dehydrogenase, an enzyme necessary for the breakdown of lysine, hydroxylysine, and tryptophan, causes an accumulation of glutaric and 3ohglutaric acid, which are intermediates in the amino acid catabolism.
It is important that an individual with ga 1 remains on treatment for life. Orotic aciduria type i oa1 is diagnosed by a urine test that reveals very high amounts of orotic acid, with milder elevations of orotidine. Glutaric aciduria ga1 the building blocks of protein are called amino acids. Glutaric aciduria type i gai is one such condition and it is one of the treatable iem. Glutaric aciduria is an inherited metabolic disease that involves the metabolism of three amino acids. On initial presentation at 6 months of age, the patient demonstrated bilateral subdural hemorrhages and widening of. In ga1, the body is unable to break down 3 amino acids called lysine, hydroxylysine and tryptophan, which then build up in the body and can cause problems. It has a highly variable clinical presentation, and laboratory investigations are not always diagnostic. Glutaric aciduria type ii is an autosomal recessive disease caused by changes mutations in the etfa subunit alpha, etfb subunit beta or etfdh genes. Amino acids are the constituent units of proteins and are therefore daily taken as part of ones diet. 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. Organic acids refer to the amino acids and certain oddchained fatty acids which are affected by these. Glutaric aciduria type 1 is a leukodystrophy that can be subclassified as an organic acidopathy.
Introduction glutaric aciduria type 1 ga1 is an autosomal recessive disorder caused by deficiency of glutarylcoa dehydrogenase, which is the key mitochondrial enzyme involved in the final degradation of lysine, l. We present detailed clinical, neuroradiologic, molecular, biochemical, and functional data on 77 patients with ga1 representative of a 14. The nervous system is especially sensitive to the effects of excess ammonia. Management of glutaric aciduria type 1 there is no cure for ga 1, but it can be managed with a modified diet, medication and special medical formulas specifically designed for persons with ga 1. Glutaric acidemia type i genetic and rare diseases. A diseasechanging intervention for glutaric aciduria type 1. Glutaric aciduria type 1 glutaric acidemia type 1 ga1 is a rare hereditary metabolic disorder with an autosomal recessive mode of inheritance. The modified diet for ga 1 is low in lysine and tryptophan. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and. There is an increased incidence in the amish, the ojibway population of canada, and people with swedish ancestry. A novel etfb mutation in a patient with glutaric aciduria type ii. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids.
In ga1, due to the lack of an enzyme, the body cannot properly deal with two of the amino acids, lysine and tryptophan. People with ga1 dont make enough of one of the enzymes needed to break down certain amino acids found in the proteins we eat. The metabolism of lysine, hydroxylysine, and tryptophan is blocked, leading to accumulation of glutaric acid ga and increased urinary concentrations of ga and 3. The biochemical hallmark of glutaric aciduria type i ga i due to glutarylcoa dehydrogenase deficiency is the accumulation of glutaric acid, and to a lesser degree of 3hydroxyglutaric and. Glutaric aciduria type 1 ga 1 is a rare inherited neurometabolic disorder due to enzymatic block in the common degradation pathway for lysine and tryptophan. The phenotypic spectrum of untreated glutaric acidemia type 1 ga1 ranges from the more common form infantileonset disease to the less common form lateronset disease i. Glutaric aciduria type 1 an overview sciencedirect topics. It is a cause of crippling striatal necrosis during infancy strauss et al.
Glutaric aciduria type 1 ga1 is a rare lifethreatening genetic disorder present from birth. Individuals with glutaric aciduria type 1 should be on a lysinefree and lowtryptophan diet. It results in the accumulation of 3hydroxyglutaric and glutaric acid. Glutaric aciduria type i, emergency treatment, pakistani children. Of note, the ga1 phenotype can vary widely between untreated family members with the same genotype, primarily as a function of the age at which the first acute encephalopathic crisis. The case of a 9monthold girl with glutaric aciduria type 1 ga 1 is reported. Metabolic acidosis was found in patients blood and organic acids in the urine which confirm the diagnosis of glutaric aciduria. It means the body cant process certain amino acids building blocks of protein, causing a harmful buildup of substances in the blood and urine. Nutrition support of infants and toddlers with glutaric aciduria type i. Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type i. Genetic testing of the umps gene is also available.
The buildup of these chemicals can damage the brain, especially the area of the brain called the. Glutaric aciduria type 1 glutaric aciduria type 1 ga1 is a rare metabolic disorder that belongs to a group of conditions known as organic acidaemias. Glutaric aciduria type i is a rare inherited disorder caused by the deficiency of glutarylcoa dehydrogenase, resulting in the accumulation of lysine and tryptophan causing progressive neurological deterioration. Glutaric aciduria type i and kynurenine pathway metabolites. The symptoms of ga1 are due to the buildup of these amino acids and their metabolites in the body, primarily affecting the brain. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. Find patient medical information for infant formula for glutaric aciduria type 1dhaara oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Type i glutaric aciduria ga1 results from mitochondrial matrix flavoprotein glutaryl. N r altman, m j rovira and m bauer american journal of neuroradiology september 1991, 12 5 966968. Infant formula for glutaric aciduria type 1dhaara oral. It involves defects in the glutarylcoa dehydrogenase enzyme, a protein that breaks down the amino acids lysine, hydroxylysine, and tryptophan. Organic acidemia, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branchedchain amino acids, causing a buildup of acids which are usually not present the branchedchain amino acids include isoleucine, leucine and valine.
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