title: Pyruvate dehydrogenase-E1α deficiency presenting as recurrent acute proximal muscle weakness of upper and lower extremities in an 8-year-old boy.
abstract: The mitochondrial pyruvate dehydrogenase enzyme complex (PDHC) plays an important role in aerobic energy metabolism and acid-base equilibrium. PDHC contains of 5 enzymes, 3 catalytic (E1, E2, E3) and 2 regulatory, as well as 3 cofactors and an additional protein (E3-binding protein) encoded by nuclear genes. The clinical presentation of PDHC deficiency ranges from fatal neonatal lactic acidosis to chronic neurologic dysfunction without lactic acidosis. Paroxysmal neurologic problems such as intermittent ataxia, episodic weakness, exercise-induced dystonia and recurrent demyelination may also be seen although they are rare. Here, we present an 8-year-old boy complaining of acute proximal muscle weakness of upper and lower extremities with normal mental status. He had a history of Guillain-Barré-like syndrome at the age of 2 years. Electrophysiologic studies showed sensorial polyneuropathy findings in the first attack and sensorimotor axonal polyneuropathy findings in the last attack. The genetic analysis revealed a previously reported hemizygote novel mutation of the PDHA1 gene (p.A353T/c.1057G > A), which encodes the E1α subunit of PDHC. Thiamine was ordered (15 mg/kg/day), dietary carbohydrates were restricted and clinical findings improved in a few weeks. This rare phenotype of PDHC deficiency is discussed.
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Umuttepe, Kocaeli 41380, Turkey. Electronic address: bkuskudar@gmail.com.
authors.forename: Bülent
authors.initials: B
authors.lastname: Kara
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Umuttepe, Kocaeli 41380, Turkey.
authors.forename: Hülya Maraş
authors.initials: HM
authors.lastname: Genç
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Umuttepe, Kocaeli 41380, Turkey.
authors.forename: Emek
authors.initials: E
authors.lastname: Uyur-Yalçın
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Umuttepe, Kocaeli 41380, Turkey.
authors.forename: Ayfer
authors.initials: A
authors.lastname: Sakarya-Güneş
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Umuttepe, Kocaeli 41380, Turkey.
authors.forename: Uğur
authors.initials: U
authors.lastname: Topçu
authors.affiliation: Department of Neurology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Mülayim
authors.affiliation: Intergen Genetic Centre, Ankara, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Ceylaner
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000503:physiopathology*; D002648:Child; D005121:Extremities / Q000503:physiopathology*; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology*; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000172:deficiency*
chemical_list: D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: Acute weakness; Guillain–Barré syndrome-like disease; PDHA1gene; Proximal muscle weakness; Pyruvate dehydrogenase-E1α deficiency