Genetic and biochemical study in a patient with glutaric acidemia type I.
Glutaryl-CoA dehydrogenase (GCDH) deficiency causes glutaric academia type I (GA-I), an inborn error of metabolism that is characterized clinically by dystonia and dyskinesia and pathologically by neural degeneration of the caudate nucleus and putamen. We report a case of GA-I in a 4-year-old boy. Analysis of blood acylcarnitines by tandem mass spectrometry (MS/MS) revealed a high concentration of glutarylcarnitine in the blood (0.59 microM). Organic acid analysis of urine via gas chromatography mass spectrometry revealed glutaric acid and 3-hydroxyglutaric acids. In order to search for mutations, the GCDH gene of the patient and his parents were amplified by polymerase chain reaction and subjected to direct sequencing. Two mutations were detected in the patient's GCDH gene. One was located in exon 7 (T713C), which caused a codon 238 leucine to proline substitution; the other was located in intron 10 (IVS10-2 A-to-C), and caused a splicing variation in intron 10 and exon 11. Genetic amniocentesis was requested when the patient's mother became pregnant again, but the fetus did not carry any mutation. Tandem mass spectrometry was successfully used to make the diagnosis of GA-I in this case via identification of genetic mutation. If GA-I can be diagnosed in the early onset or presymptomatic stage, effective therapy would reduce sequelae.
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Wei-De
WD
Lin
Chung-Hsing
CH
Wang
Chien-Chen
CC
Lai
Cheng-Chung
CC
Lee
Fuu-Jen
FJ
Tsai
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D002675:Child, Preschool; D005977:Glutarates / Q000652:urine; D050770:Glutaryl-CoA Dehydrogenase; D006801:Humans; D008297:Male; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency*
C108959:3-hydroxyglutaric acid; D005977:Glutarates; C116917:acylcarnitine; C053168:glutarylcarnitine; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid; D002331:Carnitine