title: L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability.
abstract: We report clinical and molecular studies in three unrelated Tunisian families containing seven patients with L2HGA. Although the age of onset is similar in all these patients at nearly 6 years, they progressively developed peculiar clinical phenotypes different from family to family. The three patients of family 1 showed mental retardation, epilepsy, cerebellar ataxia and pyramidal and pseudobulbar syndromes. The two patients of family 2 showed mental retardation and parkinsonism especially extrapyramidal stiffness, dystonia and myoclonus. The two patients of family 3 showed an intermediate phenotype; they share some clinical signs of the patients of family 1 (epilepsy, pyramidal and extrapyramidal syndromes) and some clinical signs of the patients of family 2 (extrapyramidal stiffness and dystonia). Molecular study identified a novel homozygous c.185C>A, p.A62D mutation on the L2HGDH gene in families 1 and 3 and the already known homozygous c.241A>G, p.K81E mutation in family 2. We suppose that the type of mutation in the L2HGDH gene does not play a complete role in the inter-familial phenotype variability. Disturbance of other unknown metabolic pathways related to L2HGA may contribute to this phenomenon.
authors.affiliation: Service of Neurology and Laboratory of Molecular Biology, National Institute of Neurology, La Rabta 1007, Tunis, Tunisia. abdelmajid.larnaout@rns.tn
authors.forename: A
authors.initials: A
authors.lastname: Larnaout
authors.forename: R
authors.initials: R
authors.lastname: Amouri
authors.forename: M
authors.initials: M
authors.lastname: Kefi
authors.forename: F
authors.initials: F
authors.lastname: Hentati
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D001483:Base Sequence; D020739:Brain Diseases, Metabolic, Inborn / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D014416:Tunisia; D055815:Young Adult
chemical_list: D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human
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