Related Experiment Video

Updated: May 26, 2026

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry
06:53

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry

Published on: November 23, 2011

Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and

Gaia Giribaldi1, Laura Doria-Lamba, Roberta Biancheri

  • 1Department of Neuroscience, Ophthalmology and Genetics, Child Neuropsychiatry Unit, G. Gaslini Institute, and University of Genoa, Genoa, Italy. gaiagiribaldi@ospedale-gaslini.ge.it

Developmental Medicine and Child Neurology
|December 7, 2011
PubMed

Insights

Pyruvate dehydrogenase complex deficiency can cause reversible brain lesions, particularly in children. Early neuroimaging during acute episodes is crucial for accurate diagnosis and timely treatment of this rare encephalomyopathy.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Genetics

Background:

  • Pyruvate dehydrogenase complex (PDHC) deficiency is a group of inherited metabolic disorders leading to encephalomyopathies.
  • These disorders manifest in various forms, including neonatal, early infantile, Leigh syndrome-like, and later-onset presentations.
  • Long-term clinical and radiological outcomes in PDHC deficiency are not fully understood.

Observation:

  • A 12-year-old male with intermittent-relapsing PDHC deficiency experienced three acute metabolic decompensation episodes over seven years.
  • Neuroimaging revealed transient, reversible signal abnormalities in the basal ganglia, inferior olivary nuclei, periaqueductal grey matter, and dentate nuclei.
  • Magnetic resonance spectroscopy confirmed the presence of lactate in affected brain regions.

Findings:

  • Molecular analysis identified a novel hemizygous c.1045G>A mutation in PDH1A, predicting a p.A349T missense mutation.
  • The patient showed clinical improvement with thiamine supplementation, tolerating febrile episodes without neurological compromise.
  • This case highlights that brain lesions in PDHC deficiency can be reversible, emphasizing the diagnostic value of neuroimaging during acute phases.

Implications:

  • Prompt neuroimaging during acute metabolic decompensation is vital for diagnosing PDHC deficiency.
  • Recognizing the potential reversibility of brain lesions can prevent misdiagnosis and treatment delays.
  • This case underscores the importance of genetic analysis and targeted therapy, such as thiamine supplementation, in managing PDHC deficiency.

More Related Videos

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues08:36

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues

Published on: May 26, 2018

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Inborn Errors of Metabolism01:20

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
Hepatic Encephalopathy01:29

Hepatic Encephalopathy

DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic shunting—including...
Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Diabetic Ketoacidosis ll: Pathophysiology01:22

Diabetic Ketoacidosis ll: Pathophysiology

Diabetic ketoacidosis (DKA) is a metabolic emergency characterized by hyperglycemia, ketonemia, and metabolic acidosis. It results from severe insulin deficiency and an excess of counterregulatory hormones, leading to uncontrolled lipolysis, ketogenesis, and widespread electrolyte and fluid disturbances.Pathophysiology The central event in DKA is a profound loss of insulin action. Without insulin, glucose uptake in insulin-dependent tissues is impaired, while hepatic glucose production...