Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing

@article{Ciara2016DifficultiesIR,
  title={Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing},
  author={Elżbieta Ciara and Dariusz Rokicki and Paulina Halat and Agnieszka Karkucinska-Wieckowska and Dorota Piekutowska-Abramczuk and Johannes A. Mayr and Joanna Trubicka and Tamara Szymańska-Dębińska and Maciej Pronicki and Magdalena Pajdowska and Magdalena Dudzińska and Maria Giżewska and Małgorzata Krajewska-Walasek and Janusz Książyk and Wolfgang Sperl and Rafał Płoski and Ewa Pronicka},
  journal={Molecular Genetics and Metabolism Reports},
  year={2016},
  volume={7},
  pages={70 - 76}
}

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References

SHOWING 1-10 OF 26 REFERENCES
Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1α subunit
TLDR
14 additional patients with total PDH complex deficiency are identified, all of whom were found to contain mutations within the PDHA1 gene (E1α subunit), which illustrates the variability in phenotype for a given gene defect.
First characterization of a large deletion of the PDHA 1 gene.
Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype.
A cognitively normal PDH-deficient 18-year-old man carrying the R263G mutation in the PDHA1 gene
TLDR
A case with a previously known common mutation in PDHA1 (R263G) with an excellent outcome at 18 years of age is reported, including now an example of a cognitively normal adult with PDH deficiency.
The spectrum of pyruvate oxidation defects in the diagnosis of mitochondrial disorders
TLDR
Patients identified by a systematic survey of the literature and patients diagnosed recently by genetic high throughput screening approaches with a pyruvate oxidation disorder and a genetically proven defect were included in the study.
Mutations in the X‐linked pyruvate dehydrogenase (E1) α subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency
TLDR
The major factors that contribute to the clinical variation in E1α deficiency and its resemblance to a recessive disease are developmental lethality in some males with severe mutations and the pattern of X‐inactivation in females.
Mutations in the gene for the E1β subunit: a novel cause of pyruvate dehydrogenase deficiency
We describe two unrelated patients with pyruvate dehydrogenase (PDH) deficiency attributable to mutations in the gene encoding the E1β subunit of the complex. This is a previously unrecognised form
Pyruvate dehydrogenase deficiency presenting as isolated paroxysmal exercise induced dystonia successfully reversed with thiamine supplementation. Case report and mini-review.
  • C. Castiglioni, D. Verrigni, M. Miranda
  • Medicine, Psychology
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 2015
Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency.
...
...