Autopsy Findings in Pyruvate Dehydrogenase E1α Deficiency: Case Report

Takahashi, Satoru; Oki, Junichi; Miyamoto, Akie; Tokumitsu, Aya; Obata, Masahiko; Ogawa, Katsuhiro; Tokusashi, Yoshihiko; Saijo, Harumi; Okuno, Akimasa

doi:10.1177/088307389701200812

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…13 Furthermore, a number of genetically determined metabolic disorders can severely disrupt neuronal migration and/or brain organization, such as lethal neonatal carnitine palmitoyltransferase II deficiency, 14 Zellweger syndrome, 15 type II glutaricacidemia, 16,17 and pyruvate dehydrogenase E 1 ␣ deficiency. [18][19][20] We recently reported the case of a girl with congenital hydranencephalic-hydrocephalic syndrome in association with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the mitochondrial respiratory chain. 21 Subsequently, the second pregnancy of the same mother terminated in an elective abortion on detection of progressive hydrocephalus in gestation week 19.…”

Section: Congenital Hydranencephalic-hydrocephalic Syndrome With Prolmentioning

confidence: 99%

“…12 A few cases appeared to be caused by defects in embryogenesis and consequent cell migration disorders. [18][19][20] We recently reported the case of a girl with congenital hydranencephalic-hydrocephalic syndrome in association with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the mitochondrial respiratory chain. [18][19][20] We recently reported the case of a girl with congenital hydranencephalic-hydrocephalic syndrome in association with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the mitochondrial respiratory chain.…”

Section: Introductionmentioning

confidence: 99%

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Congenital Hydranencephalic-Hydrocephalic Syndrome With Proliferative Vasculopathy: A Possible Relation With Mitochondrial Dysfunction

et al. 2001

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We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an elective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ultrasonography examinations performed at gestation weeks 5, 10, and 15, and negative results were obtained in standard serologic and polymerase chain reaction (PCR) tests for prenatal infections of the mother. However, the ultrasonography examination at gestation week 18 revealed hydrocephalus, in response to which the parents requested an abortion, which was performed at gestation week 20; the fetus was male and with no evident external malformations. Histopathologic studies of the brain and medulla oblongata revealed proliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negative for prenatal infections. In view of the precedent of a sister with mitochondrial dysfunction, these findings raise the pos sibility that at least some cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.

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Section: Congenital Hydranencephalic-hydrocephalic Syndrome With Prolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Congenital Hydranencephalic-Hydrocephalic Syndrome With Proliferative Vasculopathy: A Possible Relation With Mitochondrial Dysfunction

et al. 2001

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“…SAS was associated with hypoplasia/agenesis of the medullary pyramids and total/partial agenesis of the CC. The brain abnormalies were consistent with L1 syndrome (Bicker‐Adams syndrome) due to mutation in L1CAM gene (Adle‐Biassette et al, ) or L1 syndrome phenocopy due to mutation in PDHA1 gene (Takahashi et al, ; Zand et al, ). It is noteworthy that the L1CAM mutation could not be detected in one case presenting with a typical phenotype.…”

Section: Discussionmentioning

confidence: 89%

Fetal Cerebral Ventricular Dilatation: Etiopathogenic Study of 130 Observations

Darouich

Boutaud

Bessières

et al. 2017

Birth Defects Research

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The neuropathological analysis is a powerful tool in the diagnosis of the fetal CVD pathogenic mechanisms and to identify homogeneous groups. The paucity of molecular diagnosis, notably in the major groups of midbrain/hindbrain patterning defects and hemorrhagic and perfusion failure, highlights the needs of future research to improve our current knowledge on CVD causes. Birth Defects Research 109:1586-1595, 2017. © 2017 Wiley Periodicals, Inc.

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“…The clinical manifestations of PDHC deficiency in female subjects vary remarkably because mutations are present in one of the two X‐chromosomes in affected female subjects. Possible brain malformations identifiable on imaging include complete or partial agenesis of the corpus callosum, heterotopic gray matter, absence of the medullary pyramids and abnormalities of the olives, hydrocephalus, and cerebellar dysplasia 5–8 …”

Section: Discussionmentioning

confidence: 99%

“…Possible brain malformations identifiable on imaging include complete or partial agenesis of the corpus callosum, heterotopic gray matter, absence of the medullary pyramids and abnormalities of the olives, hydrocephalus, and cerebellar dysplasia. [5][6][7][8] In some patients West syndrome occurs due to brain malformations and metabolic abnormalities, such as PDHC deficiency. Wada et al reported that the mechanism of infantile spasms may be linked to mosaicism of the mutations in cerebral neurons.…”

Section: Discussionmentioning

confidence: 99%

Novel mutation (R263X) of the E1α subunit in pyruvate dehydrogenase complex deficiency

Sato

Ioi

Kashiwagi

et al. 2010

Pediatrics International

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Key words acidemia, pyruvate dehydrogenase complex, pyruvate dehydrogenase complex deficiency, PDHA1, West syndrome.The human pyruvate dehydrogenase complex (PDHC), which is localized in the mitochondrial matrix, catalyzes the thiaminedependent decarboxylation of pyruvate to acetyl-CoA. It plays an important role in the energy metabolism of the cell because it is an essential and rate-limiting enzyme that links glycolysis with the tricarboxylic acid cycle and oxidative phosphorylation. The majority of PDHC deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) a subunit gene. 1 The clinical symptoms of patients with a PDHC deficiency can vary considerably and range from intermittent ataxia to a progressive disease with mental retardation and neurological complications, or an early neonatal presentation with severe lactic acidosis and early death. In severely affected female subjects, unfavorable X-inactivation patterns may lead to severe neonatal lactic acidosis with associated structural and functional brain anomalies.We herein describe a case of PDHC deficiency in a female patient with a novel nonsense mutation (R263X) in the X-linked pyruvate dehydrogenase (E1) a subunit gene (PDHA1). Case reportA 36-year-old woman became pregnant by in vitro fertilization. At 41 weeks of gestation an ultrasound indicated hydrocephalus in the fetus. She gave birth to a girl and the infant's birthweight was 2004 g, length was 51 cm, head circumference was 32 cm, and Apgar scores were 3 at 1 min and 8 at 5 min. During the neonatal period she was hypotonic with weak suction. The family history was negative for neurologic disease. Magnetic resonance imaging (MRI; Fig. 1) of the brain at 6 months of age indicated severe cortical atrophy with ventricular enlargement, hydrocephalus and agenesis of the corpus callosum. At 7 months of age the infant had microcephaly, a narrow forehead, nasal hypoplasia, axial hypotonia, epileptic seizures and an umbilical hernia. Blood lactate (7.63 mmol/L; normal range < 2 mmol/L) and pyruvate concentrations (0.65 mmol/L; normal range < 0.19 mmol/L) were elevated, although the lactate/pyruvate ratio was normal.The cerebrospinal fluid (CSF) lactate concentration (8.37 mmol/L) was also higher than the normal range (<2 mmol/ L). Electroencephalogram demonstrated modified hypsarrhythmia, and she was diagnosed with West syndrome. The patient consequently received 220 mg/day thiamine. The patient did not respond to the thiamine administration and had no reductions in blood lactate or CSF lactate concentrations. The patient had microcephaly and mental retardation when she was reevaluated at 2 years of age. We decided to screen her for PDHC deficiency because she had a global developmental delay with high lactate concentration level and MRI features indicative of PDHC deficiency.

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Autopsy Findings in Pyruvate Dehydrogenase E1α Deficiency: Case Report

Abstract: to a severe state, causing death.2o,21 Therefore, the prolonged administration of valproic acid is thought to be the cause of acute pancreatitis in this case.

Cited by 9 publications

References 18 publications

Congenital Hydranencephalic-Hydrocephalic Syndrome With Proliferative Vasculopathy: A Possible Relation With Mitochondrial Dysfunction

Congenital Hydranencephalic-Hydrocephalic Syndrome With Proliferative Vasculopathy: A Possible Relation With Mitochondrial Dysfunction

Fetal Cerebral Ventricular Dilatation: Etiopathogenic Study of 130 Observations

Novel mutation (R263X) of the E1α subunit in pyruvate dehydrogenase complex deficiency

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