Mutations of The E3 Beta Subunit of The Pyruvate Dehydrogenase (PDH) Complex Gene: A Case Report

Introduction: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and metabolic disturbance. Most cases occur as a result of mutations in the gene for the E1α subunit of the complex (>80%). Dihydrolipoamide dehydrogenase (E3) and E3 binding protein (E3BP) defects contribute significantly to the total number of patients with PDH deficiency. Neurological features of PDH deficienc vary widely from acute encephalopathy associated with severe neonatal lactic acidosis in infancy and early childhood. Case: Fourteen-year-old girl was admitted due to intractable seizures. She was the second child of healthy parents who were first-degree cousins. She was born at term with a birth weight of 3.3 kg. Her neonatal period was unremarkable. At nine months of age, she was admitted with developmental delay. Her seizures started when she was 1 year old. On physical examination, the patient showed hyperreflexia, spasticity, hypertonicity and could not walk independently. At the time of assessment, she had lactic acidosis, with a blood lactate concentration of 4,84 mmol/L. Urine organic acid showed lactic acid 1401mmol/molkr (35-131), pyruvic acid 526 mmol/molkr (3,5-17,3) excretion. Brain magnetic resonance imaging at 14 years showed diffusion-restriction in bilateral putamen. A homozygous pathogenic mutation c.1336C>T (p.Arg446Ter) was found in PDHX gene. Conclusion: The varied clinical presentation can lead to a delayed diagnosis. We herein present a sporadic case of PDH deficiency, a delayed diagnosis and identification of the specific gene mutation that caused dysfunction of the PDHX gene with the use of clinical exome sequencing (CES).
Keywords: Pyruvate dehydrogenase deficiency; lactic acidosis