ArticleJournal of inherited metabolic disease2009
PDH E1β deficiency with novel mutations in two patients with Leigh syndrome.
Article in Journal of inherited metabolic disease, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Targeted Therapies for Leigh Syndrome: Systematic Review and Steps Towards a 'Treatabolome'.Journal of neuromuscular diseases · 2021Pooled it
- Consensus Guidelines for Diagnosis and Management of Pyruvate Dehydrogenase Complex Deficiency.Journal of inherited metabolic disease · 2026Review
- Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.Children (Basel, Switzerland) · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Clinical exome sequencing reveals a mutation in PDHA1 in Leigh syndrome: A case of a Chinese boy with lethal neuropathy.Molecular genetics & genomic medicine · 2021Article
- Leigh Syndrome: A Tale of Two Genomes.Frontiers in physiology · 2021Review
- Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q10 content.European journal of human genetics : EJHG · 2016Article
- Molecular Characterization and Transcriptional Regulation Analysis of the Bovine PDHB Gene.PloS one · 2016Article
- The spectrum of pyruvate oxidation defects in the diagnosis of mitochondrial disorders.Journal of inherited metabolic disease · 2015Review
- Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.Nature genetics · 2015Article
- Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects.Annals of clinical and translational neurology · 2014Article
- The genetics of Leigh syndrome and its implications for clinical practice and risk management.The application of clinical genetics · 2014Review
- The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.Molecular genetics and metabolism · 2012Article
- The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.Molecular genetics and metabolism · 2012Review
- Distinct retinal deficits in a zebrafish pyruvate dehydrogenase-deficient mutant.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome.Molecular neurobiology · 2010Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the PDHA1 gene which encodes the E(1)α subunit, with few cases of mutations in the genes for E(3), E3BP (E(3) binding protein), E(2) and E(1)-phosphatase being reported. Only seven patients with deficiency of the E(1)β subunit have been described, with mutations in the PDHB gene in six of them. Clinically they presented with a non-specific encephalomyopathy. We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E(1) activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. Sequencing of PDHB revealed a homozygous point mutation (c.302T>C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). All three mutations appear to destabilize the E(1) enzyme with a decrease of both E(1)α and E(1)β subunits in immunoblot analysis. To our knowledge, these patients with novel PDHB mutations are the first reported with Leigh syndrome.
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Registered trials
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