Tracing the origin of L-2-hydroxyglutaric aciduria in a family.
We describe late diagnosis of an adult with L-2-hydroxyglutaric aciduria (MIM 236792) on the basis of characteristic metabolite data and mutation analysis in the L2HGDH gene. The patient lacked MRI abnormalities which have been purported to be constant or typical findings in this disease. We further report the genetic status of his parents and his one living sibling. Our observations underline the clinical heterogeneity of the syndrome of L-2-hydroxyglutaric aciduria. This report emphasizes the diagnostic benefit of the assessment of urinary organic acids not only in children, but also in adult patients with unexplained neurological symptoms. The patient was determined to be compound heterozygous for two novel missense mutations in exon 4 of the gene (c.418G>C, c.446T>G), resulting in amino acid exchanges from alanine to proline (p.Ala140Pro) and leucine to arginine (p.Leu149Arg), respectively. The mother of our patient was heterozygous for Ala140Pro, and the father heterozygous for Leu149Arg only. Mutation analysis of a healthy 49-year-old third son of the non-consanguineous parents revealed a normal exon 4.
Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany.
Jörn Oliver
JO
Sass
Janet S
JS
Romrell
Sarah Y
SY
Vinson
Hubert H
HH
Fernandez
Judith
J
Fischer
Ramon L
RL
Rodriguez
Michael S
MS
Okun
D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004185:Disability Evaluation; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005977:Glutarates / Q000032:analysis / Q000652:urine; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense / Q000235:genetics; D009460:Neurologic Examination
D005819:Genetic Markers; D005977:Glutarates; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human