Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria
Document Type
Article
Publication Date
3-2010
Department
Department of Biological Sciences
Abstract
We performed molecular, enzyme, and metabolic studies in 50 patients with D-2-hydroxyglutaric aciduria (D-2-HGA) who accumulated D-2-hydroxyglutarate (D-2-HG) in physiological fluids. Presumed pathogenic mutations were detected in 24 of 50 patients in the D-2-hydroxyglutarate dehydrogenase (D2HGDH) gene, which encodes D-2-hydroxyglutarate dehydrogenase (D-2-HGDH). Enzyme assay of D-2-HGDH confirmed that all patients with mutations had impaired enzyme activity, whereas patients with D-2-HGA whose enzyme activity was normal did not have mutations. Significantly lower D-2-HG concentrations in body fluids were observed in mutation-positive D-2-HGA patients than in mutation-negative patients. These results imply that multiple genetic loci may be associated with hyperexcretion of D-2-HG. Accordingly, we suggest a new classification: D-2-HGA Type I associates with D-2-HGDH deficiency, whereas idiopathic D-2-HGA manifests with normal D-2-HGDH activity and higher D-2-HG levels in body fluids compared with Type I patients. It remains possible that several classifications for idiopathic D-2-HGA patients with diverse genetic loci will be revealed in future studies.
Publication Title
Human Mutation
Recommended Citation
Kranendijk, M.,
Struys, E.,
Gibson, K.,
Wickenhagen, W.,
Abdenur, J.,
Buechner, J.,
Christensen, E.,
De Kremer, R.,
Errami, A.,
Gissen, P.,
Gradowska, W.,
Hobson, E.,
Islam, L.,
Korman, S.,
Kurczynski, T.,
Maranda, B.,
Meli, C.,
Rizzo, C.,
Sansaricq, C.,
Trefz, F.,
Webster, R.,
Jakobs, C.,
&
Salomons, G.
(2010).
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria.
Human Mutation,
31(3), 279-283.
http://doi.org/10.1002/humu.21186
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/3657