Pyruvate dehydrogenase-E1α deficiency presenting as generalized dystonia: A genetic diagnosis with important clinical implications

• Published in: Clinical neurology and neurosurgery Vol. 241; p. 108307
• Main Authors: Kowalska, Agata, Figura, Monika, Zawadka, Mateusz, Koziorowski, Dariusz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2024; Elsevier Limited
• Subjects: Acidosis; Ataxia; Binding sites; Cerebrospinal fluid; Child development; Children; Consciousness; Deep brain stimulation; Dehydrogenases; Dysarthria; Dystonia; Editing; Genetic screening; Globus pallidus; Lactic acidosis; Levodopa; Magnetic resonance imaging; Mutation; Patients; Pyruvate dehydrogenase (lipoamide); Pyruvate dehydrogenase-E1α deficiency; Pyruvic acid; Strabismus; Vitamin B; Deep brain stimulation; Dystonia; Pyruvate dehydrogenase-E1α deficiency
• ISSN: 0303-8467; 1872-6968
• DOI: 10.1016/j.clineuro.2024.108307

Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disease mostly associated with severe lactic acidosis, rapid progression of neurological symptoms and death during childhood. We present a 33-year-old male with PDC deficiency caused by a Val262Leu mutation in PDHA1gene. He demonstrated generalized dystonia affecting trunk and upper extremities and paraparesis as the most significant features, with onset of symptoms at age 8. Brain MRI showed bilaterally increased signal within the globus pallidus, typical of Leigh syndrome. A periodic lactate increase in serum and cerebrospinal fluid was detected. We describe a case of pyruvate dehydrogenase deficiency being diagnosed only 25 years after the onset of symptoms and highlight PDHC deficiency as a possible cause of treatable dystonia in childhood, which may respond well to thiamine and levodopa treatment.
•33-year-old male patient with pyruvate dehydrogenase complex deficiency (PDCD) caused by a mutation in the PDHA1 gene.•Clinical features of generalized dystonia affecting trunk and upper extremities and paraparesis.•Treatment with DBS unsuccessful- possibly due to damage of globus pallidus in PDCD- implication for target selection.•Brain MRI showing bilaterally increased signal within the globus pallidus, consistent with Leigh syndrome.•Highlighting PDHC deficiency as a possible cause of treatable dystonia in childhood.