Genetics of Pyruvate Carboxylase Deficiency Workup

Updated: Mar 15, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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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.