An interesting case of metabolic dystonia: L-2 hydroxyglutaric aciduria

Balaji, Padma; Venkataraman, Viswanathan; Chellathurai, Amarnath; Panigrahi, Debasis

doi:10.4103/0972-2327.128565

Cited by 8 publications

(6 citation statements)

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“…Atypical presentations such as dystonia, anxiety, autism, status epilepticus, and acute hemiplegia hemi convulsion epilepsy syndrome (HHE) have been reported. [12-16] One child in our series presented with febrile status epilepticus. While the largest case series does not describe an acute presentation, there are several case reports of L2HGA with severe neonatal encephalopathy, sudden death in infancy, encephalopathy with rapid functional decline following seizures, and trauma.…”

Section: Discussionmentioning

confidence: 99%

“…There have been reports of significant clinical response with riboflavin. [12,13,33,34] Treatment response might be influenced by the residual enzyme activity based on the type of mutation, though a consistent correlation has not been established. Genetic workup done in one child in our series revealed a homozygous missense variation in exon 10 of L2HGDH gene; this child is stable on treatment with no seizure recurrence and has developmental gains at 6-month follow-up.…”

Section: Discussionmentioning

confidence: 99%

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Clinicoradiological Spectrum of L-2-Hydroxy Glutaric Aciduria: Typical and Atypical Findings in an Indian Cohort

Muthusamy

Sudhakar

Christudass

et al. 2019

JCIS

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Context: Neurometabolic disorders form an important group of potentially treatable diseases. It is important to recognize the clinical phenotype and characteristic imaging patterns to make an early diagnosis and initiate appropriate treatment. L-2-hydroxy glutaric aciduria (L2HGA) is a rare organic aciduria with a consistent and highly characteristic imaging pattern, which clinches the diagnosis in most cases. Aims: The study aims to describe the clinical profile, magnetic resonance imaging (MRI) patterns, and outcome in a cohort of children with L2HGA and to assess the clinicoradiological correlation. Materials and Methods: This is a retrospective descriptive study done at the Department of Radiodiagnosis and Neurological Sciences of our institution. Clinical and radiological findings of children diagnosed with L2HGA over an 8-year period (2010–2017) were collected and analyzed. Descriptive statistical analysis of clinical and imaging data was performed. Results: There were six girls and four boys. A total of 14 MRI brain studies in 10 patients with the diagnosis were analyzed. MRI of all patients showed a similar pattern with extensive confluent subcortical white-matter signal changes with symmetrical involvement of dentate nuclei and basal ganglia. In two children who presented with acute decompensation, there was asymmetric cortical involvement and restricted diffusion, which are previously unreported. There was no significant correlation between the radiological pattern with the disease duration, clinical features, or course of the disease. Conclusion: MRI findings in L2HGA are highly consistent and diagnostic, which helps in early diagnosis, particularly in resource-constraint settings, where detailed metabolic workup is not possible. The article also describes novel clinical radiological profile of acute encephalopathic clinical presentation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinicoradiological Spectrum of L-2-Hydroxy Glutaric Aciduria: Typical and Atypical Findings in an Indian Cohort

Muthusamy

Sudhakar

Christudass

et al. 2019

JCIS

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“…L-2-Hydroxyglutaric aciduria (L-2-HGA; OMIM 236792) is a rare organic aciduria that was first described by Duran in 1980 [ 1 ]; this neurometabolic disease is inherited as an autosomal recessive mode. Approximately 300 cases have been reported worldwide (as of 2014) [ 2 ]. The diagnosis of L-2-HGA can be made based on clinical evaluation, magnetic resonance imaging (MRI), urinary organic acid screening by gas chromatography-mass spectrometry (GC-MS), and mutational analysis of L-2-hydroxyglutarate dehydrogenase ( L2HGDH ) gene.…”

Section: Introductionmentioning

confidence: 99%

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria

Wei

Yang

et al. 2018

BMC Med Genet

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BackgroundL-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons.Case presentationWe presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic.ConclusionWe predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.

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“…Although the most common initial presentation reported by Barth and colleagues were walking delay and gait abnormality (6 out of 8 patients), movement disorders may be under-recognized [ 2 ]. Balaji et al recently described 2 siblings with L2HGA, one of which with dystonia of the head, trunk and upper extremities, the other with dystonia of distal upper and lower extremities [ 5 ]. In our patient (proband), the initial presentation that prompted her parents to bring her to medical attention was writer’s cramp.…”

Section: Discussionmentioning

confidence: 99%

Writer’s cramp as a presentation of L-2-hydroxyglutaric aciduria

Termsarasab

2014

J Clin Mov Disord

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L-2-hydroxyglutaric aciduria (L2HGA) is a neurometabolic disorder characterized by macrocephaly, seizures, progressive mental retardation, pyramidal signs, ataxia and tremor. Dystonia is an under-recognized feature of this entity in the literature. We report two siblings with L2HGA, one of whom presented with writer’s cramp followed by dystonia of the other hand. An elevated plasma lysine, highly elevated urine 2-hydroxyglutaric acid, and MRI with characteristic findings (leukoencephalopathy of bilateral subcortical white matter sparing central white matter) suggested the diagnosis, which was confirmed by genetic testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s40734-014-0009-9) contains supplementary material, which is available to authorized users.

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An interesting case of metabolic dystonia: L-2 hydroxyglutaric aciduria

Cited by 8 publications

References 10 publications

Clinicoradiological Spectrum of L-2-Hydroxy Glutaric Aciduria: Typical and Atypical Findings in an Indian Cohort

Clinicoradiological Spectrum of L-2-Hydroxy Glutaric Aciduria: Typical and Atypical Findings in an Indian Cohort

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria

Writer’s cramp as a presentation of L-2-hydroxyglutaric aciduria

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