l -2-Hydroxyglutaric aciduria: two Japanese adult cases in one family

Fujitake, Junko; Ishikawa, Yasuhiro; Fujii, Hayato; Nishimura, K; Hayakawa, Katsumi; Inoue, Fumio; Terada, Naoto; Okochi, Masakazu; Tatsuoka, Yoshihisa

doi:10.1007/s004150050367

Cited by 31 publications

(16 citation statements)

References 19 publications

(9 reference statements)

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“…Because the exact time of onset in these two patients is unknown, they were not included in the mean age of onset. The cases in the literature reported as adult onset [Fujitake et al, 1999;Goffette et al, 2006] were diagnosed during adulthood but, in retrospect, the patients also had symptoms during childhood. In fact, the disease has an insidious onset and it is therefore not possible to pinpoint a specific time of onset.…”

Section: Clinical Phenotypementioning

confidence: 99%

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study

et al. 2010

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L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n 5 106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondiseaserelated variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/ patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.

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Section: Clinical Phenotypementioning

confidence: 99%

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study

et al. 2010

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“…L2HGA with mild phenotype has been previously described [2,14]. However, acute unprovoked decompensation as may occur in other aminoacidopathies, and occurred in this case, has not been previously described in L2HGA.…”

Section: Sirsmentioning

confidence: 44%

“…There are less than 20 adult reports of L2HGA (average age at time of diagnosis 30; age range at time of diagnosis 18-57), with all patients having a history of developmental delay in childhood [1][2][3][4][5][6][7][8]. L2HGA typically presents in the first year of life with non-specific motor delay and later cognitive and motor developmental delay in childhood [1,9].…”

Section: Sirsmentioning

confidence: 99%

l-2-Hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration

et al. 2009

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“…The information currently available on mutations underlying L-2-HGA provides no evidence for a correlation of individual mutations with the spectrum or severity of clinical symptoms. Notably, in clinical reports on siblings with L-2-OH-GA, including one case with proven homozygosity for the same mutation (Rzem et al 2004), pronounced differences in the clinical presentation have been observed (Fujitake et al 1999;Goffette et al 2006). A better understanding of interacting factors in the pathway of L2HGDH will be necessary for a better understanding of the influences on the phenotype.…”

Section: Discussionmentioning

confidence: 92%

L‐2‐Hydroxyglutaric aciduria: Identification of ten novel mutations in the L2HGDH gene

Sass

Jobard

Topçu

et al. 2008

J of Inher Metab Disea

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L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene. The clinical presentation of individuals with L-2-HGA is somewhat variable, but affected individuals typically suffer from progressive neurodegeneration. Analysis of urinary organic acids reveals an increased signal of 2-hydroxyglutaric acid, mainly as the L-enantiomer. L-2-HGA is known to occur in individuals of various ethnic backgrounds, but up to now mutation analysis has been mainly focused on patients of Turkish and Portuguese origin. This led us to confirm the diagnosis on the DNA level and undertake the corresponding mutation analysis in individuals of diverse ethnicity previously diagnosed with L-2-HGA on the basis of urinary metabolites and clinical/neuroimaging data. In 24 individuals from 17 families with diverse ethnic and geographic origins, 13 different mutations were found, 10 of which have not been reported previously. At least eight of the patients were compound heterozygotes. The identification of two mutations (c.751C > T and c.905C > T in exon 7) in patients with different origins supports the view that they occurred independently in different families. In contrast, the mutation c.788C > T was detected in all six Venezuelan patients originating from the same Caribbean island of Margarita, but not in other patients, thus rendering a founder effect likely. None of the mutations was found in the control population, indicating that they are most probably causative. Mutation analysis may improve the quality of diagnosis and prenatal diagnosis of L-2-HGA.

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l -2-Hydroxyglutaric aciduria: two Japanese adult cases in one family

Cited by 31 publications

References 19 publications

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study

l-2-Hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration

L‐2‐Hydroxyglutaric aciduria: Identification of ten novel mutations in the L2HGDH gene

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