Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children

Ivanov, Ivan S., Azmanov, Dimitar N., Ivanova, Mariya B., Chamova, Teodora, Pacheva, Ilyana H., Panova, Margarita V., Song, Sharon, Morar, Bharti, Yordanova, Ralitsa V., Galabova, Fani K., Sotkova, Iglika G., Linev, Alexandar J., Bitchev, Stoyan, Shearwood, Anne-Marie J., Kancheva, Dalia, Gabrikova, Dana, Karcagi, Veronika, Guergueltcheva, Velina, Geneva, Ina E., Bozhinova, Veneta, Stoyanova, Vili K., Kremensky, Ivo, Jordanova, Albena, Savov, Aleksey, Horvath, Rita, Brown, Matthew A., Tournev, Ivailo, Filipovska, Aleksandra, & Kalaydjieva, Luba (2014) Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. Molecular Genetics and Metabolism, 113(1-2), pp. 76-83.

View at publisher (open access)


Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population.

The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history.

We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families.

Impact and interest:

2 citations in Scopus
Search Google Scholar™
3 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 89121
Item Type: Journal Article
Refereed: Yes
Keywords: Congenital lactic acidosis; PDHX; Roma/Gypsy founder mutation
DOI: 10.1016/j.ymgme.2014.07.017
ISSN: 1096-7192
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Crown Copyright © 2014
Deposited On: 14 Oct 2015 22:30
Last Modified: 16 Feb 2016 04:35

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page