PDHC - Clinical: Pyruvate Dehydrogenase Complex (PDHC), Fibroblasts

Test Catalog

Test Name

Test ID: PDHC    
Pyruvate Dehydrogenase Complex (PDHC), Fibroblasts

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of patients with a clinical suspicion of a pyruvate dehydrogenase complex deficiency or an energy metabolism disorder

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This assay is intended to detect decreases in total pyruvate dehydrogenase complex (PDHC) activity; it is not designed to detect cases of pyruvate dehydrogenase (PDH) kinase or phosphatase deficiencies.


This test is not available for prenatal testing.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, a fibroblast culture and cryopreservation for biochemical studies will always be performed at an additional charge. However, for multiple lysosomal enzyme assays on a patient utilizing fibroblast culture, only 1 culture is required regardless of the number of enzyme assays ordered. If viable cells are not obtained within 30 days, client will be notified.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The pyruvate dehydrogenase complex (PDHC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, a critical step in the production of cellular energy. PDHC is a multienzyme complex located in the inner mitochondrial membrane, consisting of 6 different components: pyruvate decarboxylase (E1, with alpha and beta subunits), dihydrolipoic transacetylase (E2), dihydrolipoyl dehydrogenase (E3), 2 regulatory enzymes (PDH kinase and PDH phosphatase), and E3-binding protein.


PDHC deficiency is a mitochondrial disorder with a variable clinical presentation ranging from fatal congenital lactic acidosis to relatively mild ataxia or neuropathy. In infants and children with PDHC deficiency, the most common features are delayed development and hypotonia, as well as acquired microcephaly. Seizures and ataxia are also frequent features. Less common manifestations include congenital brain malformations, particularly ventriculomegaly and agenesis of the corpus callosum, or degenerative changes, including Leigh disease. Facial dysmorphism is seen in a small portion of patients. PDHC deficiency is one of the most common causes of primary lactic acidosis in children. The severity of the disease progression is thought to be related to the severity of the lactic acidosis as well as the level of residual enzyme activity.


PDHC deficiency can be caused by defects in the E1 alpha, E1 beta, E2, or E3 subunits. The most common cause of PDHC deficiency is a defect in the E1 alpha gene, located on the X chromosome. Both females and males with an E1 alpha gene mutation are affected with PDHC deficiency, thus it is classified as X-linked dominant. Mutations in the E1 alpha gene are typically de novo.


The most important initial diagnostic test is the measurement of blood and cerebrospinal fluid lactate and pyruvate, along with a lactate-to-pyruvate (L:P) ratio (typically normal ratio with elevated lactate and pyruvate). Additionally, plasma amino acids (AAQP / Amino Acids, Quantitative, Plasma) may detect an increase in alanine. A diagnosis of PDHC deficiency depends on the measurement of enzyme activity in cells or tissues, most commonly in skin fibroblasts.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

>25.00 nmol/min/g protein (Normal)

5.00-25.00 nmol/min/g protein (Indeterminate)

<5.00 nmol/min/g protein (Deficient)

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

When below-normal enzyme activities are detected, a detailed interpretation is given. This interpretation includes an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, and recommendations for additional biochemical testing.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay is intended to detect decreases in total pyruvate dehydrogenase complex (PDHC) activity; it is not designed to detect cases of pyruvate dehydrogenase kinase or phosphatase deficiencies.


Additional testing is necessary to determine the specific defect in the pyruvate dehydrogenase complex.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Patel KP, Obrien TW, Subramony SH, et al: The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 2012;106:385-394

2. Robinson BH: Lactic acidemia: In Disorders of Pyruvate Carboxylase and Pyruvate Dehydrogenase. Edited by D Valle, AL Beaudet, B Vogelstein, et al: New York. McGraw-Hill, 2014. Accessed March 30, 2017. Available at www.ommbid.mhmedical.com/content.aspx?sectionid=62633368&bookid=971&jumpsectionID=62633403&Resultclick=2.

4. Lib M, Rodriguez-Mari A, Marusich MF, Capaldi RA: Immunocapture and microplate-based activity measurement of mammalian pyruvate dehydrogenase complex. Anal Biochem 2003 Mar 1;314(1):121-127. PMID:12633610

Special Instructions and Forms Library of PDFs including pertinent information and consent forms, specimen collection and preparation information, test algorithms, and other information pertinent to test