Pyruvate Dehydrogenase Deficiency (PDCD) Workup

Updated: Aug 17, 2018
  • Author: Richard E Frye, MD, PhD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Laboratory Studies

The following studies are indicated in pyruvate dehydrogenase complex (PDC) deficiency (PDCD):

Lactate and pyruvate levels

High blood lactate and pyruvate levels with or without lactic acidemia suggest an inborn error of metabolism at the mitochondrial level.

Cerebrospinal fluid also shows elevation of lactate and pyruvate (at times even in the absence of elevated blood levels).

In mild cases of pyruvate dehydrogenase complex deficiency, blood lactate and pyruvate levels may be elevated only slightly or not at all under normal conditions; elevated levels are usually found during periods of crisis.

A recent study suggests that the lactate-to-pyruvate ratio is only diagnostically useful to differentiate pyruvate dehydrogenase complex deficiency from other forms of congenital lactic acidosis at higher lactate levels (>5 mmol/L). [8]

Serum and urine analysis

Serum and urine amino acid analyses reveal hyperalaninemia.

Deficiency of the E3 enzyme also causes an elevation in branched-chain amino acids in the serum and alpha-ketoglutarate in the serum and urine.

Amino acid levels vary with the general metabolic state of the patient; a catabolic state, in which gluconeogenesis is activated and proteins are degraded, elevates many amino acids, leading to a nonspecific amino acid profile.

Hyperammonemia and nonspecific amino acid elevation are associated with E2 enzyme deficiency, which is more common during acute illnesses.

Thiamine pyrophosphate-adenosine triphosphate phosphoryl transferase inhibitor can be detected in urine or blood by a specific assay.

Other studies

Definitive diagnosis is made by showing abnormal enzyme function.

Functional assays can be performed on leukocytes, fibroblasts, or properly preserved tissue samples. Pyruvate dehydrogenase complex activity should be measured with and without thiamine in order to detect cases of thiamine-responsive pyruvate dehydrogenase complex deficiency.

Blood and fibroblast enzyme tests are the easiest to obtain, but mosaicism can cause normal enzymatic activity in leukocytes and fibroblasts, requiring a tissue biopsy if the diagnosis is strongly suspected.

A skin sample grows if obtained within 2 days of death.


Imaging Studies


MRI shortly after birth may reveal ventricular dilation, cerebral atrophy, hydranencephaly, partial or complete absence of the corpus callosum, absence of the medullary pyramids, or abnormal and ectopic inferior olives.

MRI of infants with progressive neurological symptoms may reveal symmetric cystic lesions and gliosis in the cortex, basal ganglia, brainstem, or cerebellum, or generalized hypomyelination.

Individuals with a deficiency in the E2 subunit may reveal discrete lesions restricted to the globus pallidus.

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS) of the brain reveals high lactate levels in individuals with pyruvate dehydrogenase complex deficiency.

N -acetylaspartate and choline levels are consistent with hypomyelination.


Histologic Findings

Histologic findings of Leigh syndrome may be found in an autopsy examination.