Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

Mild Phenotype in a Male with Pyruvate Dehydrogenase Complex Deficiency Associated with Novel Hemizygous In-Frame Duplication of the E1α Subunit Gene (PDHA1)


Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that occurs most commonly due to mutations in the X-linked E1α subunit gene (PDHA1). We report a novel duplication of PDHA1 associated with a mild phenotype in a 15-year-old boy who was diagnosed with PDHC deficiency at 4 years of age following a history of seizures and lactic acidosis. The novel c.1087_1119 mutation in exon 11 resulted in an in-frame duplication of 11 amino acids. Measurements of PDHC activity in cultured skin fibroblasts were low, corresponding to 18.6 and 11.6% of the mean with respect to prior controls, whereas the E1 PDH component was absent. He has borderline intellectual functioning and maintains normal lactate levels on a ketogenic diet in between relapses due to illness. Review of the literature reveals wide variation of clinical phenotype in patients with mutations of the E1α subunit gene (PDHA1). There appears to be a higher incidence of normal or borderline intellectual ability in individuals who have insertions or deletions that are in-frame versus those that are out-of-frame. Furthermore, there is no correlation between mean residual PDH activity and phenotype in these patients.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View