Recurrent and novel mutations of GCDH gene in Chinese glutaric acidemia type I families

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation

“…Macrocephaly, characteristic neuroimaging findings and urine organic acid analysis suggested the diagnosis of GA-I. Molecular genetic testing confirmed that she was compound heterozygote for the common R402W (c.1204C>T) mutation and the novel mutation IVS10-2A>G (c.1244A>G) at the same nucleotide position as the IVS10-2A>C mutation previously reported exclusively in Far Eastern populations (Busquets et al 2000a;Tang et al 2000;Shu et al 2003).…”

“…Despite the paucisymptomatic status of this patient, MRI showed white matter disease. Molecular genetic analysis of the GCDH revealed compound heterozygosity for the common R402W (p.Arg402Trp) mutation and a novel mutation, IVS10-2A>G, at a nucleotide position previously known to be mutated (IVS10-2A>C) exclusively in patients of Chinese/ Taiwanese origin (Busquets et al 2000a;Tang et al 2000;Shu et al 2003). Based on the results of urine organic acid analysis, the patient being a high excretor of GA and 3OHGA, we could only deduce a genotype-biochemical phenotype correlation, and we hypothesize that the novel pathogenic mutation in the GCDH gene described in this case report (c.1244A>G transversion; IVS10-2A>G) does not alleviate the effect of the common R402W mutation on residual GCDH activity and metabolite excretory profile.…”

“…The GCDH gene is located on chromosome 19p13.2, is 7 kb large, contains 11 exons and 10 introns, and codes for a polypeptide product of 438 amino acids, from which the functional GCDH is derived after cleavage of the 44-amino acids N-terminal targeting sequence following import into the mitochondrial matrix (Koeller et al 1995;Schwartz et al 1998). More than 150 pathogenic mutations have been identified of which the most frequent mutation in Caucasians is R402W (c.1204C>T) found in up to 10-20% of alleles, while the IVS10-2A>C mutation is found almost exclusively in patients of Chinese/Taiwanese origin (Strauss et al 2003;K€ olker et al 2006aBusquets et al 2000a;Tang et al 2000;Shu et al 2003).…”

Perioperative Management of a Patient With Glutaric Aciduria

“…The disorder generally presents in early childhood with the majority of children having no measurable enzyme activity. The estimated prevalence varies from 1 in 30,000 newborns in one Scandinavian study to 1 in 30,000 -100,000 newborns in other studies [2][3][4][5]. The prevalence may be much higher in isolated populations in the Middle East countries due to higher rates of consanguinity [6,7].…”

Glutaric Acidemia Type 1: A Case of Infantile Stroke

“…Mutations in the glutaryl-CoA dehydrogenase (GCDH) gene result in glutaryl-CoA dehydrogenase (Enzyme Commission number 1.3.8.6) deficiency which is a key enzyme in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. The estimated prevalence is 1 in 30,000-100,000 newborns whereas this prevalence might be much higher in some countries with high rates of consanguineous marriages (Tang et al 2000;Strauss et al 2003;K€ olker et al 2006Baradaran et al 2014). GCDH deficiency is characterized by increased levels of organic acid excretions; namely of glutaric acid, 3-hydroxyglutaric acid (3-OHGA), glutaconic acid in urine and glutarylcarnitine in plasma.…”