To describe the pattern of magnetic resonance mr imaging abnormalities in l2hydroxyglutaric aciduria l2hga and to evaluate the correlation between imaging abnormalities and disease duration. Three years later, two novel inborn errors of metabolism were. We describe some novel clinical and molecular characteristics found in a boy with l 2 hydroxyglutaric aciduria. L 2 hydroxyglutaric aciduria is a metabolic disorder in which l 2 hydroxyglutarate accumulates as a result of a deficiency in fadlinked l 2 hydroxyglutarate dehydrogenase, a mitochondrial enzyme. Two pakistani siblings with l2hydroxyglutaric aciduria are reported herein. Attention deficit hyperactivity disorder comorbidity in an adolescent diagnosed with l2 hydroxyglutaric aciduria and response to atomoxetine treatment. L 2 hydroxyglutaric aciduria l2hga is a rare neurometabolic disorder with an autosomal recessive mode of inheritance. There was a severe anaemia, which reacted well to iron supplements. A report of 29 patients article pdf available in the turkish journal of pediatrics 471. A 6yearold male and a 2yearold female, born to consanguineous parents, had chronic slowly progressive neurodegenerative disorder with insidious onset after infancy. L2hydroxyglutaric aciduria radiology reference article. D 2 hga and l 2 hga have each been reported to affect fewer than 150 individuals worldwide. L 2 hydroxyglutaric aciduria was first reported in 1980 2, and there has since been about 295 cases described in the literature 1.
Increasing evidence suggests that patients with l2hga have a predisposition to cerebral neoplasms. Hga is a neurometabolic disorder that produces a variety of clinical neurological deficits in humans, including psychomotor retardation in the early years of life, progressive cerebellar dysfunction ataxia and intention tremor, learning disability and in some cases seizures. Hemiconvulsionhemiplegiaepilepsy syndrome as a presenting. The centripetal pattern of white matter involvement limits the differential diagnosis. Several clinical descriptions have appeared on l 2 hydroxyglutaric aciduria l 2 hga since the index case reported in 1980. Hydroxyglutaric aciduria in staffordshire bull terriers wiley online. Staffordshire bull terriers with l 2 hydroxyglutaric aciduria are commonly ataxic, have abnormal posture and show muscle cramping. Mri of childhood epilepsy due to inborn errors of metabolism. A 5yearold boy, excreting large amounts of 2hydroxyglutaric acid in the urine 3. What information about a genetic condition can statistics provide. A wide range of inborn errors of metabolism leading to neona tal onset. Aug 01, 2002 two pakistani siblings with l 2hydroxyglutaric aciduria are reported herein. Introduction l 2 hydroxyglutaric aciduria l 2 hga is an autosomal recessive neurometabolic disease with a slowly progressive course and characterized by increased levels of hydroxyglutaric acid in urine, cerebrospinal fluid and plasma. Treatment is focused on alleviating the signs and symptoms of the condition, such as medications to control seizures.
Attention deficit hyperactivity disorder comorbidity in an adolescent diagnosed with l 2 hydroxyglutaric aciduria and response to atomoxetine treatment. The l 2 form is more common, severe, and mainly affects the central nervous system. L2 hydroxyglutaric aciduria l2hga is an inherited neurometabolic disorder affecting dogs. Pdf hosted at the radboud repository of the radboud. The absence of brainstem involvement in l 2 hydroxyglutaric aciduria is an important differentiating. For additional information about this publication click this link. It is characterized by elevated levels of l 2 hydroxyglutarate in urine, cerebrospinal fluid, and, to a lesser extent, plasma. Diagnosis is based on the presence of an excess of l 2 hydroxyglutaric acid in urine, blood and cerebrospinal fluid. It belongs in a group of such disorders called 2 hydroxyglutaric aciduria.
Journal of inherited metabolic disease, 21, 251254. The major types of this disorder are called d 2 hydroxyglutaric aciduria d 2 hga, l 2 hydroxyglutaric aciduria l 2 hga, and combined d, l 2 hydroxyglutaric aciduria d, l 2 hga. Symptoms exhibited by affected individuals include cerebellar ataxia, seizures, hypotonia and macrocephaly in most cases. Mental regression and seizures were evident in both patients, whereas cerebellar dysfunction was the main motor handicap in the male and pyramidal. L2hydroxyglutaric aciduria in two siblings request pdf. Identification of novel l2hgdh gene mutations and update. L 2 hydroxyglutaric aciduria is a rare autosomal recessive encephalopathy caused by mutations in the l 2 hydroxyglutarate dehydrogenase gene. L2hydroxyglutaric aciduria and lactic acidosis article pdf available in journal of inherited metabolic disease 2. Acute hemiconvulsionhemiplegiaepilepsy syndrome has not been reported as a presenting feature in l 2 hydroxyglutaric aciduria. Duran m, kamerling jp, bakker hd, van gennip ah, wadman sk. L 2 hydroxyglutaric aciduria results from mutations in duranin l2hgdh gene. Clinical and magnetic resonance imaging features of l2hydroxyglutaric aciduria academia.
In this condition clinical features mainly consist of mental deterioration, ataxia and motor deficits. L2hydroxyglutaric aciduria, a defect of metabolite repair. The combined d, l 2 hydroxyglutaric aciduria is caused by mutations in the slc25a1 gene, which is inherited in an autosomal recessive manner autosomal dominant. This may be related to the pathologic accumulation of l2hg because high amounts of 2 hg have been found in brain neoplasms that have idh1 mutations. L 2 hydroxyglutaric aciduria l 2 hga is a rare, neurodegenerative, slowly progressing and autosomal recessively inherited metabolic disorder. Genetic counseling l 2 hydroxyglutaric aciduria follows an autosomal recessive pattern of inheritance. Pattern of mr imaging abnormalities in 56 patients, abstract purpose. Topcu m, erdem g, saatci i, aktan g, simsek aa, renda y, schutgens rbh, wanders rja, jacobs c. The patient presented with psychomotor retardation and dystrophy. L2hydroxyglutaric aciduria is caused by changes mutations in the l2hgdh gene and is inherited in an autosomal recessive manner. A novel compound heterozygous mutation in a chinese boy with. Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a nonsex chromosome.
L 2 hydroxyglutaric aciduria is an autosomal recessive encephalopathy including neurological traits such as psychomotor impairment, seizures and ataxia. L 2 hydroxyglutaric aciduria l2hga, a neurometabolic disorder caused by mutations in the l2 hydroxyglutarate dehydrogenase l2hgdh gene, presents with psychomotor retardation, cerebellar ataxia, extrapyramidal symptoms, macrocephaly and seizures. Caesarean section was performed, as an elective procedure, because of the fetal malpresentation. The underlying metabolic defect in l 2 hydroxyglutaric aciduria is unknown. White matter abnormalities in an adult patient with l2. The disease progresses with mental retardation, behavioral disorder, ataxia, extrapyramidal signs and epileptic seizures. The major types of this disorder are called d2hydroxyglutaric aciduria d2hga, l2hydroxyglutaric aciduria l2hga, and combined d, l2hydroxyglutaric aciduria d, l2hga. Combined d 2 and l 2 hydroxyglutaric aciduria d 2 hg and l 2 hg is an autosomal recessive neurometabolic disorder characterized by neonatalonset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Pdf hosted at the radboud repository of the radboud university nijmegen the following full text is a publishers version.
Request pdf l2hydroxyglutaric aciduria in staffordshire bull terriers l2hydroxyglutaric aciduria is an inborn error of metabolism, which. L 2 hydroxyglutaric aciduria is a rare autosomal recessive disorder associated with progressive brain damage. Prenatal diagnosis can be performed by mutational analysis and by the measurement of l 2 hydroxyglutaric acid in amniotic fluid. A single case of l 2 hydroxyglutaric aciduria described by and colleagueschen 1996 in a neonate with fatal disease bears similarities to our case in various regards, including neonatal seizures, lactic acidosis and destructive changes in the. Attention deficit hyperactivity disorder comorbidity in an. L2hydroxyglutaric aciduria is an inborn error of metabolism, which has been recognized in humans since 1980. Why is l2 hydroxyglutaric aciduria relevant for a general. L2hydroxyglutaric aciduria, a defect of metabolite.
L2hydroxyglutaric aciduria is a metabolic disorder in which l2hydroxyglutarate accumulates as a result of a deficiency in fadlinked l2hydroxyglutarate dehydrogenase, a mitochondrial enzyme. L 2 hydroxyglutaric aciduria and lactic acidosis article pdf available in journal of inherited metabolic disease 2. Oct 28, 2015 l 2 hydroxyglutaric aciduria is an inherited metabolic condition that is associated with progressive brain damage. L 2 hydroxyglutaric aciduria padma balaji 1, v viswanathan 1, amarnath chellathurai 2, debasis panigrahi 1 1 department of pediatric neurology, childs trust medical research foundation and kanchi kamakoti childs trust hospital, chennai,tamil nadu, india 2 department of radiodiagnosis, government stanley medical college, chennai, tamil nadu, india. Combined d2 and l2hydroxyglutaric aciduria with neonatal. A rare autosomal recessive disorder clinically characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate to severe mental retardation. Management and treatment there is currently no specific treatment for l 2 hydroxyglutaric aciduria. Birth weight was 2800 g, birth length 50 cm and head circumference 36 cm. These disorders can be classified into two groups, d 2 hga and l 2 hga. The purpose of this pictorial essay is to classify epilepsy syndromes due to inborn errors of metabolism according to age at onset and type of seizure and to show the mri features of man. In this study, we identified compound heterozygous variants of l2hgdh in an adult patient with epilepsy and intellectual disability. L 2 hydroxyglutaric aciduria causes a variety of signs, not all appear in every dog.
These signs are easy to document and some helpful videos have been published online. Apr 07, 2017 2 hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. Glutaric aciduria type 1 encephalopathy or movement disorders with. Progress in understanding 2hydroxyglutaric acidurias ncbi. Affected dogs have a mutation in the enzyme that breaks down l2hydroxyglutaric acid resulting in increased levels of l2hydroxyglutaric acid in urine, blood and cerebrospinal fluid and progressive damage to the brain. What this paper adds this paper provides a concise summary of the major inborn errors of metabolism iems which may present with epilepsy, categorized by age at presentation.
Hga was first recognised in 1980 and has the biochemical. The offspring of poorly controlled or unrecognised phenylketonuria pku have. L2hydroxyglutaric aciduria in staffordshire bull terriers request. Inborn errors of metabolism causing epilepsy rahman.
We report an 8yearold chinese boy, who had characteristic developmental delay, ataxia and acrocephaly as the main symptoms. Our experience, on the basis of 11 previously unreported cases of l2hga, 3 of which developed cerebral neoplasms during the course of. Signs and symptoms of this condition typically begin during infancy or early childhood and may include developmental delay, seizures, speech difficulties, macrocephaly and abnormalities in a part of the brain called the cerebellum, which is involved in coordinating movement i. L2 hydroxyglutaric aciduria is a neurodegenerative disorder with insidious onset after infancy, which is likely inherited in an autosomal recessive mode, characterized by mental retardation.
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