July 23, 2020 0 By admin

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. Request PDF on ResearchGate | Aciduria glutárica tipo I: Descripción del primer Type I glutaric aciduria is an inherited genetic disorder caused by a defect Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and . A Acidemia Glutarica tipo-1 e um dos erros inatos do metabolismo diagnosticados com maior frequencia na Colombia. E consequencia de uma alteracao no.

Author: Munris Melkis
Country: Saudi Arabia
Language: English (Spanish)
Genre: Sex
Published (Last): 24 February 2017
Pages: 389
PDF File Size: 2.4 Mb
ePub File Size: 3.37 Mb
ISBN: 215-6-32830-240-7
Downloads: 94952
Price: Free* [*Free Regsitration Required]
Uploader: Faesida

CC HPO: Glutaric acidemia I is an glufarica recessive metabolic disorder characterized by gliosis and neuronal loss in the basal ganglia and a progressive movement disorder that usually begins during the first year of life Goodman et al. The glutaric aciduria was increased by oral administration of L-lysine, which is metabolized through glutaryl-CoA, and was decreased by reduced protein intake.

Metabolism of radioactive glutaryl-CoA was deficient in white cells, a result compatible with inherited deficiency aciuria glutaryl-CoA dehydrogenase Goodman et al. The urine contained large amounts of glutaric acid. From a review of this and 4 cases reported earlier, the authors concluded that disorders in the metabolism of organic acids should be sought in patients with progressive dystonic palsy. Lysed leukocytes from their patient showed severe impairment in the ability to metabolize glutaryl-CoA.

All had a unique pattern of frontotemporal atrophy on computerized tomography CT. Remarkably, in both sib pairs, 1 child was asymptomatic. All 12 previously reported patients had a homogeneous phenotype presenting in infancy with debilitating dystonia and choreoathetosis. In an affected infant with glutaric aciduria, Mandel et al. CT changes preceded the onset of symptoms by 3 months.

Improvement in the temporal lobe atrophy was observed after a period of treatment, coincident with marked clinical improvement. In 10 patients, the disorder was first manifest between 3 and 18 months during an acute infectious illness. Four of these children died in early childhood, also during acute illnesses.

However, there had been little progression of the neurologic disorder after age 5 years in the surviving children, and intellect was usually preserved even in children with severe spastic paralysis. They suggested that restriction of dietary protein and limitation of protein catabolism, dehydration, and acidosis during illnesses may prevent the onset or progression of neurologic disease in Amish patients with this disorder. The oldest patient was a year-old man who was normal until age 3 months when, after a period of irritability and poor feeding on day 7 of a varicella infection, he experienced an acute, afebrile episode of lgutarica posturing and thereafter became flaccid and unresponsive.

After recovery from the acute episode, which was diagnosed as varicella encephalitis, he was left with a residual spastic diplegia, partial bulbar palsy, and choreoathetosis. Despite spastic diplegia and moderate choreoathetosis, he had normal intelligence and regularly worked in a carriage and harness repair shop. There had been no apparent progression of his neurologic disease since the single damaging illness at age 3 months.

Ten had a glutaricq dystonic-dyskinetic disorder, 1 had a mild hyperkinetic disorder, and 1 was asymptomatic. Two children died in a state of hyperthermia. Tio deficiency and malnutrition developed in patients with severe dystonia and dysphagia, which necessitated replacement therapy and gastrostomy.

Dieta vegetariana en aciduria glutárica tipo I | Anales de Pediatría

A slowly progressive dyskinetic disorder developed in 1 subject despite adequate early dietary treatment. Macrocephaly was found in 3. Computed tomography and magnetic resonance investigations in 10 showed deep bitemporal spaces in 7. Neuropsychologic testing of tippo of 12 subjects demonstrated receptive language function to be superior to expressive language and motor function, although cognitive functions were less affected than motor functions.


The metabolic symptoms, gglutarica as hypoglycemia and metabolic acidosis, were minimal. After recovery the children had lost most motor skills and functioned at a 1- to 2-month-old level. At that point, the very distinctive clinical picture of a severe dystonic-dyskinetic syndrome in alert-looking children with relatively well-preserved intellectual functions and a prominent forehead could be recognized.

Glutaric aciduria type 1

About one-fourth of the patients never suffered encephalopathic crisis but presented with subacute motor delay. Gluarica patients showed developmental delay from birth and a progressive dystonic ‘cerebral palsy. High levels of glutaric acid were seen in the spinal fluid of all these patients.

The patients presented between 6 gltarica and 2 years of age with either seizures or hypotonia and dystonia. All but 1 had severe impairment of psychomotor development gltarica abnormalities on T2-weighted MRI, chiefly bilateral hyperdensities of basal ganglia, atrophy of the temporal lobe, or extensive white matter hypodensities.

The analyses showed that in patients who did not have a precipitating illness before the first appearance of motor symptoms, the age at onset was significantly associated with the severity of motor impairments and overall clinical outcome.

In patients who had a precipitating illness, the age at onset did not predict the outcome. In both groups of patients, basal ganglia degeneration, enlargement of spaces containing cerebrospinal fluid, and white matter abnormalities were indicative of a poorer prognosis.

Treatment given after the appearance of symptoms was not associated with a better clinical outcome or fewer motor deficits. In a discussion of the natural history of GA I, Strauss et al. In most neonates, an enlarged head circumference is the only presenting sign of the disorder. The authors pointed to radiologic signs of large fluid collections in the middle cranial fossae. Veins could be seen stretching tenuously across this space, where they are subject to distortion and rupture.

Acute subdural hemorrhage can occur after minor head trauma afiduria in some instances is accompanied by retinal hemorrhages. Investigation of child abuse preceded a correct metabolic diagnosis in some non-Amish children. Of the Amish patients, 17 were identified retrospectively and 20 were treated prospectively following diagnosis through screening of asymptomatic newborns. In all groups, basal ganglia degeneration was the major determinant of functional disability.

Orphanet: Aciduria glutarica tipo 1

Acute striatal necrosis was the major cause of morbidity and mortality, and dystonia caused chronic medical and surgical complications. In older patients, exercise intolerance, hypoglycemia, and seizures often developed.

The former results from carnitine deficiency, which can also give rise to myopathy, cardiomyopathy, and Reye-like hepatocerebral crisis, and the latter can occur during intercurrent illness even in carnitine-supplemented children. Subsequent evaluation revealed increased urinary glutaric acid and compound heterozygosity for mutations in the GCDH gene. The first patient had onset of headaches at age 35, developed tremor of both arms at age 50, and had 6 tonic-clonic seizures between ages 54 and At age 63, he developed ataxia, progressive dementia, and speech problems.

The other patient developed headache, vertigo, and gait disturbance at age 15 years following an upper respiratory tract infection. Both patients had macrocephaly from birth and showed supratentorial leukoencephalopathy. Genetic analysis confirmed glutaryl-CoA dehydrogenase deficiency. Clinical treatment resulted in improvement and full recovery, respectively. Despite early diagnosis, one-third of Amish infants with glutaryl-CoA dehydrogenase deficiency developed striatal lesions that leave them permanently disabled.

To better understand mechanisms of striatal degeneration, Strauss et al. Asymptomatic infants had reduced glucose tracer uptake and increased blood volume throughout the gray matter, which may signify predisposition to brain injury. Acute striatal necrosis consisted of 3 stages: Neither had macrocephaly, organomegaly, cognitive impairment, or acute encephalopathy in childhood.


Laboratory studies showed decreased long-chain acylcarnitines and high excretion of 3-hydroxyglutaric acid, but urinary glutaric acid excretion was normal. Brain imaging showed increased signals in the lenticular nuclei.

The findings implicated mitochondrial fatty acid metabolism as an important pathway in the development of dystonia, and Marti-Masso et al. Recommendations included a lysine-restricted diet to reduce the accumulation of the neurotoxic metabolites glutaric acid, 3-hydroxyglutaric acid, and glutaryl-CoA deriving from the precursor amino acid lysine; the supplementation of carnitine to prevent secondary carnitine depletion, to facilitate production of the nontoxic C5DC, and to replenish the intracellular free coenzyme A pool; and the intermittent and stepwise intensification of metabolic treatment using a high-calorie, low- or no-protein emergency treatment protocol during putatively threatening episodes such as infectious disease to prevent striatal injury.

Outcome was evaluated in relationship to therapy and therapy-independent parameters. According to following the guidelines of Kolker et al. In patients suspected of having the disorder, repeated examinations of organic acids in the urine and enzyme assay may be necessary to confirm the diagnosis.

In 1 case in which the fetus was unaffected, glutaric acid was not detected in the amniotic fluid at amniocentesis 15 weeks and the glutaryl-CoA dehydrogenase activity of cultured amniotic cells was normal. In the other case, there was a marked increase of glutaric acid in the amniotic fluid as well as a deficiency of glutaryl-CoA dehydrogenase in cultured amniotic cells.

The pregnancy was terminated, and postmortem studies confirmed the diagnosis of glutaric acidemia. Christensen described experience with chorionic villus sampling for first-trimester diagnosis of this disorder. Among 16 pregnancies, 4 were predicted to represent an affected fetus; in 3 of the affected cases, GCDH activity was measured in both uncultured and cultured chorionic cells and the correct diagnosis was established by both measurements.

Among 64 unrelated patients with glutaric acidemia type I, Biery et al. Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. Glutaric acidemia type I occurs in about 1 ininfants worldwide Hedlund et al.

Glutaric aciduria type I: Adult onset glutaric aciduria type I presenting with a leukoencephalopathy. Glutaric aciduria type 1: Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: Age at symptom onset predicts severity of motor impairment and clinical outcome of glutaric acidemia type 1. Glutaric aciduria in progressive choreo-athetosis. Prenatal diagnosis of glutaryl-CoA dehydrogenase deficiency: Antenatal diagnosis of glutaric acidemia.

There was a problem providing the content you requested

Glutaric aciduria; a ‘new’ disorder of amino acid metabolism. Glutaric acidemia type 1. Use of guidelines improves the neurological outcome in glutaric aciduria type 1. Early signs and course of disease of glutaryl-CoA dehydrogenase deficiency. Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency glutaric aciduria type I.

Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency. Dystonia and dyskinesia in glutaric aciduria type I: Exome sequencing identifies GCDH glutaryl-CoA dehydrogenase mutations as a cause of a progressive form of early-onset generalized dystonia.

Variable clinical and biochemical presentation of seven Spanish cases with glutaryl-CoA-dehydrogenase deficiency. Glutaric aciduria type 1 of the Amish. Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency. Type I glutaric aciduria, part 1: Glutaric aciduria type I misdiagnosed as Leigh’s encephalopathy and cerebral palsy.