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Title
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Founder p.Arg 446*mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children
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Author
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Abstract
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| Investigation of 31 of Roma patients with congenital lactic acidosis (CIA) 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 CIA 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. Crown Copyright (C) 2014 Published by Elsevier Inc. |
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Language
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English
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Source (journal)
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Molecular genetics and metabolism. - Orlando, Fla
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Publication
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Orlando, Fla
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2014
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ISSN
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1096-7192
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DOI
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10.1016/J.YMGME.2014.07.017
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Volume/pages
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113
:1-2
(2014)
, p. 76-83
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ISI
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000342539700015
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Pubmed ID
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25087164
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Full text (Publisher's DOI)
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Full text (open access)
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