Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Mar;37(3):177-81.
doi: 10.1136/jmg.37.3.177.

Mutation analysis in glutaric aciduria type I

J Zschocke  1 , E Quak, P Guldberg, G F Hoffmann
Affiliations

Mutation analysis in glutaric aciduria type I

J Zschocke et al. J Med Genet. 2000 Mar.

Abstract

Glutaric aciduria type 1 (GA1), resulting from the genetic deficiency of glutaryl-CoA dehydrogenase (GDH), is a relatively common cause of acute metabolic brain damage in infants. Encephalopathic crises may be prevented by carnitine supplementation and diet, but diagnosis can be difficult as some patients do not show the typical excretion of large amounts of glutaric and 3-hydroxyglutaric acids in the urine. We present a rapid and efficient denaturing gradient gel electrophoresis (DGGE) method for the identification of mutations in the glutaryl-CoA dehydrogenase (GCDH) gene that may be used for the molecular diagnosis of GA1 in a routine setting. Using this technique, we identified mutations on both alleles in 48 patients with confirmed GDH deficiency, while no mutations were detected in other patients with clinical suspicion of GA1 but normal enzyme studies. There was a total of 38 different mutations; 27 mutations were found in single patients only, and 21 mutations have not been previously reported. Fourteen mutations involved hypermutable CpG sites. The commonest GA1 mutation in Europeans is R402W, which accounts for almost 40% of alleles in patients of German origin. GCDH gene haplotypes were determined through the analysis of polymorphic markers in all families, and three CpG mutations were associated with different haplotypes, possibly reflecting independent recurrence. The high sensitivity of the DGGE method allows the rapid and cost efficient diagnosis of GA1 in instances where enzyme analyses are not available or feasible, despite the marked heterogeneity of the disease.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nature. 1986 May 15-21;321(6067):209-13 - PubMed
    1. Nucleic Acids Res. 1991 Apr 11;19(7):1427-30 - PubMed
    1. Nucleic Acids Res. 1994 Mar 11;22(5):880-1 - PubMed
    1. Hum Mol Genet. 1995 Sep;4(9):1493-8 - PubMed
    1. Neuropediatrics. 1996 Jun;27(3):115-23 - PubMed

Publication types