People with ga1 dont make enough of one of the enzymes needed to break down certain amino acids found in the proteins we eat. Riboflavinresponsive multiple acylcoa dehydrogenase. Glutaric aciduria type i ga1 is a rare hereditary metabolic disorder caused by a deficiency of the mitochondrial enzyme glutarylcoa dehydrogenase gcdh. It is a rare but important etiology of macrocephaly, with an estimated incidence of 1 in 100,000 births. Mutations in the gcdh gene cause glutaric aciduria, type 1. Glutaric aciduria type 1 radiology reference article. Glutarylcoa dehydrogenase gcdh deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Myllynen and perhomaa contributed equally to this work. The buildup of these chemicals can damage the brain, especially the area of the brain called the. L2hydroxyglutaric aciduria is a leukoencephalopathy with a consistent and characteristic mri pattern that should strongly suggest the diagnosis 3,4,6. The glutaric aciduria was increased by oral administration of llysine, which is metabolized through glutarylcoa, and was decreased by reduced protein intake. It is much more common in amish communities and in the ojibwa population of canada, where up to 1. Although conventional magnetic resonance imaging mri findings of glutaric aciduria type 1 ga1 have been well established, diffusion weighted mr imaging dwi and proton mr spectroscopy mrs findings are limited.
Pdf mr imaging findings of glutaric aciduria type ii researchgate. Proton nuclear magnetic resonance spectroscopy of body fluids in. Without enough of the enzyme, the breakdown products of these amino acids build up in tissues of the body. About 1 of every 30 000 to 40 000 people have glutaric acidemia. Glutaric aciduria type 1 ga1 is an autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by deficiency of glutarylcoa dehydrogenase. Glutaric acid definition of glutaric acid by medical. Organic acids refer to the amino acids and certain oddchained fatty acids which are affected by these. Glutaric aciduria type 1 ga1 is an organic acidaemia. Glutaric aciduria type 1 an overview sciencedirect topics. Cranial mri within 24 hr of the onset of the neurological syndrome shows focal. Glutaric aciduria or glutaric acidemia type i, an autosomal recessive disease, usually presents with an acute encephalopathic crisis in young children. Highresolution 1h nmr spectroscopy of body fluids has proved to be very useful in diagnos tics of inherited.
Despite high prognostic relevance of early diagnosis and start of metabolic treatment as well as an additional cost saving potential later in life, only a limited number of countries recommend newborn screening for gai. Glutaric acidauri, type 1 occurs in greater than1 in 75,000 caucasian live births. Glutaric aciduria type i ga1 is a rare autosomal recessive disorder affecting the catabolism of the amino acids lysine, hydroxylysine and tryptophan. In ga1, due to the lack of an enzyme, the body cannot properly deal with two of the amino acids, lysine and tryptophan.
With conventional magnetic resonance imaging, it may be useful in the diagnosis and evaluation of glutaric aciduria type 1 patients. 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 ii ga2 is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. New insights for glutaric aciduria type i brain oxford. Glutaric aciduria definition of glutaric aciduria by. Pour mixture into clean feeding bottles or container. Brain mri findings as an important diagnostic clue in glutaric aciduria type 1.
It means the body cant process certain amino acids building blocks of protein, causing a harmful buildup of substances in the blood and urine. Extrastriatal changes in patients with lateonset glutaric. Affected patients can present with brain atrophy and macrocephaly and with acute dystonia secondary to striatal degeneration in most cases triggered by an. Sensitivity and specificity of free and total glutaric acid and 3hydroxyglutaric acid measurements by stableisotope dilution assays for the diagnosis of glutaric aciduria type i.
Standard mri and multivoxel mrs were performed at 1. Children with ga1 are reported to be predisposed to subdural hematoma sdh development due to stretching of cortical veins secondary to cerebral atrophy and expansion of csf spaces. Glutaric aciduria type 1 gat 1 is an autosomal recessive inherited metabolic disease caused by the deficiency of mitochondrial enzyme, glutarylcoenzyme. Type i glutaric aciduria, part 2 wiley online library. It has a highly variable clinical presentation, and laboratory investigations are not always diagnostic. Although the related linear dicarboxylic acids adipic and succinic acids are watersoluble only to a few percent at room temperature, the watersolubility of glutaric acid is over 50% ww. Glutaric acid is naturally produced when the body digests proteins from the foods we eat, including breast milk and infant formula.
Glutaric aciduria type 1 ga1 is a rare lifethreatening genetic disorder present from birth. Ct and mr of the brain in glutaric acidemia type i. We report widespread restricted diffusion in the white matter and increased diffusion in bilateral putamen in a case of ga1. Cerebral 1h mr spectroscopy revealing white matter naa. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic metabolic acidosis. Diagnosis and management of glutaric aciduria type i. Glutaric aciduria type i diagnosis case with normal glutaryl carnitine and urine organic acid analysis.
Glutaric aciduria type i nord national organization for. Magnetic resonance imaging findings of adultonset glutaric aciduria type i. Fluoro2deoxyglucose 18 fdg pet scan of the brain in glutaric aciduria type i. Mri magnetic resonance imaging msms tandem mass spectrometry nbs newborn screening 3ohga 3hydroxyglutaric acid sdh subdural hemorrhage sign scottish intercollegiate guidelines network introduction glutaric aciduria type i gai, omim no. Characterization of novel gcdh pathogenic variants causing glutaric aciduria type. Pdf mr imaging findings of glutaric aciduria type ii. Glutaric aciduria type 1 ga1 is a rare but serious inherited condition. Magnetic resonance of myelination and myelin disorders. The objective of this study was to describe the profile of patients diagnosed with ga1 at inkosi albert luthuli central hospital, durban, south africa from 2007 to 2015. At present, the treatment for ga1 involves a protein restricted diet for life and taking regular dietary. H magnetic resonance spectroscopy 1hmrs reveals increased glutaric acid and 3ohga concentrations in the white matter. People with ga1 therefore need to restrict the amount of protein they eat. Normally, our bodies break down protein foods like meat and fish into amino acids. It is caused by defective manufacture of glutarylcoenzyme a dehydrogenase.
Clinically asymptomatic glutaric aciduria type i in a 4 512yearold girl with bilateral temporal arachnoid cysts. Type i glutaric aciduria ga1 is an inborn error of organic acid metabolism. Guideline for the diagnosis and management of glutarylcoa. The lactate resonance becomes inverted on intermediateecho mrs. Incompletely processed proteins and fats can build up, leading to a dangerous chemical imbalance called acidosis. 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. Current methods of magnetic resonance spectroscopy available for the brain. Nursing guidelines for the management of children with glutaric aciduria type 1 revision no.
Glutaric aciduria type i synonym, glutaric acidemia type i is an autosomal recessive disease caused by inherited deficiency of glutarylcoa dehydrogenase gcdh, ec 1. Glutaric aciduria type ii presenting in a teenager. Proposed recommendations for diagnosing and managing. An inherited disorder marked by multiple neurological deficits in childhood, including motor dysfunction, developmental delay, and brain atrophy. Glutaric acidemia type i ga1 is a genetic metabolic disorder. It is in the group of disorders known as cerebral organic acidemias. Our studies have shown brain glutaric acid levels in gcdhdeficient mice on a normal diet to be 500. Nunes j1, loureiro s, carvalho s, pais rp, alfaiate c, faria a, garcia p, diogo l. There is an increased incidence in the amish, the ojibway population of canada, and people with swedish ancestry.
Neurological manifestations of organic acidurias nature. Acute decompensation in children and adults with a type 1 glutaric aciduria. Biochemically, the disease is characterized by accumulation of glutaric acid, 3hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatographymass spectrometry of organic acids or tandem mass spectrometry of. Magnetic resonance spectroscopic characteristics of glutaric. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. Without neonatal initiation of treatment, 8090% of patients with glutaric aciduria type 1 ga1 develop striatal injury during the first six years of life resulting in a complex, predominantly dystonic movement disorder. This disorder is characterized by progressive dystonia and dyskinesia. Imaging, therefore, has an important role to play as the mri features can be characteristic. Glutaric acidemia type ii genetics home reference nih. Diffusionweighted mr imaging and mr spectroscopy in. Magnetic resonance spectroscopy mrs of a 12yearold female patient with glutaric aciduria type ii was compared with data obtained from four healthy age. 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.
There is wide variation in disease severity, even reported among affected siblings. Glutaric acid is the organic compound with the formula c 3 h 6 cooh 2. Brain mri findings as an important diagnostic clue in. Glutaric acidemia type ii 351 was admitted at 14 weeks of age for investigation, including cranial computed tomography ct, magnetic resonance imaging mri, and magnetic resonance spectroscopy mrs.
It has an estimated prevalence of 1 in 100,000 newborns lindner et al. Glutaric acidemia type i genetic and rare diseases. Abnormal proton magnetic resonance spectroscopy findings with organic acidemias should alert the radiologist that a neurometabolic disorder such as ga1 may be present. Glutaric acidemia is genetic disorder that affects how protein is broken down in the body. Glutaric aciduria type i gai is a rare metabolic disorder caused by inherited deficiency of glutarylcoa dehydrogenase. Glutaric acidemia type iii is a rare metabolic condition characterized by persistent, isolated accumulation or excretion of glutaric acid. The mri changes seen are bilateral and symmetrical, as would be expected from a neurometabolic disorder. Past history of febrile illness and presence of macrocrania mimic postmeningitic hydrocephalus.
Guidelines proposed recommendations for diagnosing and managing individuals with glutaric aciduria type i. Individuals with this condition have deficiency or absence of gcdh enzyme that is involved in the lysine metabolism. Proton nuclear magnetic resonance nmr spectroscopy of body fluids has been successfully. Glutaric aciduria type 1 ga1 is a rare metabolic disorder of glutarylcoadehydrogenase enzyme deficiency. Glutaric acidemia type ii is an inherited disorder that interferes with the bodys ability to break down proteins and fats to produce energy. Pdf diagnosis and management of glutaric aciduria type i.
Glutaric aciduria type 1 ga1 the building blocks of protein are called amino acids. Learn more about glutaric aciduria, type 1 from related diseases, pathways, genes and ptms with the novus bioinformatics tool. Glutaric acidemia type 2 is an autosomal recessive metabolic disorder that is characterised by defects in the ability of the body to use proteins and fats for energy. Glutaric acidemia, type 1 ga1 is a rare, inherited genetic disease. 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. Alessa m, bakheet s, patay z, alwatban j, powe j, joshi s, ozand pt. Newborn screening by tandem mass spectrometry for glutaric. L2hydroxyglutaric aciduria radiology reference article. 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. Pdf glutaric aciduria type i synonym, glutaric acidemia type i is a rare organic aciduria. Glutaric acidemia type iii genetic and rare diseases. Request pdf diffusionweighted mr imaging and mr spectroscopy in glutaric aciduria type 1 although conventional magnetic resonance imaging mri findings of glutaric aciduria type 1 ga1.
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