title: Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency.
abstract: To distinguish pyruvate dehydrogenase deficiency (PDH) from other antenatal neurometabolic disorders thereby improving prenatal diagnosis, we describe imaging findings, clinical phenotype, and brain lesions in fetuses from 3 families with molecular characterization of this condition. Neuropathological analysis was performed in 4 autopsy cases from 3 unrelated families with subsequent biochemical and molecular confirmation of PDH complex deficiency. In 2 families there were mutations in the PDHA1 gene; in the third family there was a mutation in the PDHB gene. All fetuses displayed characteristic craniofacial dysmorphism of varying severity, absence of visceral lesions, and associated encephaloclastic and developmental supra- and infratentorial lesions. Neurodevelopmental abnormalities included microcephaly, migration abnormalities (pachygyria, polymicrogyria, periventricular nodular heterotopias), and cerebellar and brainstem hypoplasia with hypoplastic dentate nuclei and pyramidal tracts. Associated clastic lesions included asymmetric leukomalacia, reactive gliosis, large pseudocysts of germinolysis, and basal ganglia calcifications. The diagnosis of PDH deficiency should be suspected antenatally with the presence of clastic and neurodevelopmental lesions and a relatively characteristic craniofacial dysmorphism. Postmortem examination is essential for excluding other closely related entities, thereby allowing for biochemical and molecular confirmation.
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Nathalie
authors: N
authors: Pirot
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Marie
authors: M
authors: Crahes
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Homa
authors: H
authors: Adle-Biassette
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Anais
authors: A
authors: Soares
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Martine
authors: M
authors: Bucourt
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Audrey
authors: A
authors: Boutron
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Lionel
authors: L
authors: Carbillon
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Cyril
authors: C
authors: Mignot
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Laetitia
authors: L
authors: Trestard
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors: Soumeya
authors: S
authors: Bekri
authors: From the Department of Radiology (NP), Pathology Laboratory (MC, AL), and Department of Metabolic Biochemistry (AS, SB), Rouen University Hospital, Rouen, France; Pathology Department (HAB), Lariboisière University Hospital, Rouen, France; Pathology Laboratory (MB), Jean Verdier University Hospital, Paris-Bondy, Rouen, France; Biochemistry and Genetics Laboratory (AB), Bicêtre University Hospital, Paris-le Kremlin Bicêtre, Paris, France; Department of Obstetrics and Gynecology (LC), Jean Verdier University Hospital, Paris-Bondy, France; Intensive Care Unit (CM), Trousseau University Hospital, Paris, France; Belvédère Maternity Hospital (LT), Mont Saint Aignan, France; and NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions (SB, AL), Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France. annie.laquerriere@chu-rouen.fr.
authors: Annie
authors: A
authors: Laquerrière
mesh_terms: D000328:Adult; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D005333:Fetus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D016216:Ultrasonography, Prenatal
chemical_list: D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit
keywords: Congenital lactic acidosis; Fetal presentation; Leigh syndrome; Molecular genetics; Neurodevelopment; Neuropathology; Pyruvate dehydrogenase deficiency.