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Genetics of Pyruvate Carboxylase Deficiency Workup

  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD  more...
Updated: Feb 18, 2016

Laboratory Studies

The following should be assessed in patients with pyruvate carboxylase deficiency (PCD):

Lactate and pyruvate levels

High blood lactate and pyruvate levels with or without a lactic aciduria suggests an inborn error of energy metabolism.

An increased lactate-to-pyruvate ratio is characteristic of citric acid cycle disorders.

This ratio may be particularly elevated during periods of crisis, such as illness or metabolic stress.


Hypoglycemia during fasting results from greatly reduced gluconeogenesis.

Period of fasting required to produce symptoms is much shorter in pyruvate carboxylase deficiency than other disorders.

Amino acid levels

Measurement of serum amino acids reveals hyperalaninemia, hypercitrullinemia, hyperlysinemia, and low aspartic acid levels.

Hyperalaninemia is due to the pyruvate shunting.

Hypercitrullinuria and hyperlysinemia result from a metabolic block in the urea cycle due to a low aspartic acid.

Low aspartic acid is due to the deficiency in the oxaloacetate precursor.

Amino acid levels vary with the general metabolic state of the patient. If the patient is in a catabolic state, proteins are degraded, resulting in the elevation of many amino acids and a nonspecific amino acid profile.

Other studies

Hyperammonemia results from poor ammonia disposal and decreased urea cycle function.

Abnormal enzyme function can be detected by functional assays performed on leukocytes, fibroblasts, or properly preserved tissue samples.

The severe form of pyruvate carboxylase deficiency can be diagnosed by demonstrating the absence of pyruvate carboxylase (PC) mRNA or specific cross-reacting material.

Cerebrospinal fluid (CSF) shows an elevation of lactate and pyruvate.

CSF glutamine is markedly reduced, whereas glutamic acid and proline levels are elevated.


Imaging Studies


Type B pyruvate carboxylase deficiency is associated with ventricular dilation, cerebrocortical and white matter atrophy, or periventricular white matter cysts.

Type A pyruvate carboxylase deficiency is associated with symmetric cystic lesions and gliosis in the cortex, basal ganglia, brainstem, or cerebellum and/or generalized hypomyelination, as well as hyperintensity of the subcortical fronto-parietal white matter.

Magnetic resonance spectroscopy (MRS)

Brain MRS shows high lactate levels, as well as levels of N -acetylaspartate and choline consistent with hypomyelination.


Histologic Findings

Histologic examination of the liver may reveal lipid droplet accumulation.

CNS neuropathology may include poor myelination, paucity of cerebral cortex neurons, gliosis, and proliferation of astrocytes.

Contributor Information and Disclosures

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.


Paul J Benke, MD, PhD Director of Clinical Genetics, Joe DiMaggio Children's Hospital

Paul J Benke, MD, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

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This is a diagrammatic representation of the citric acid cycle and the abnormalities found in pyruvate carboxylase deficiency. The dotted line represents absent pathways. Pyruvate cannot produce oxaloacetate and is shunted to alternative pathways that produce lactic acid and alanine. The lack of oxaloacetate prevents gluconeogenesis and urea cycle function.
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