Test Catalog

Test Id : PDHC

Pyruvate Dehydrogenase Complex, 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

Pyruvate dehydrogenase complex (PDHC) deficiency is a rare mitochondrial disorder with a clinical presentation consisting of metabolic and neurological components of varying severity.

 

PDHC should be considered in patients with early-onset neurological disease and unexplained lactic acidosis, especially if structural brain abnormalities are present.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

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 will always be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

PDHC: Colorimetric Enzyme Assay

CULFB: Cell Culture

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Pyruvate Dehydrogenase Comp, Fibro

Aliases
Lists additional common names for a test, as an aid in searching

PDC (Pyruvate Dehydrogenase Complex)

PDHC (Pyruvate Dehydrogenase Complex)

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 will always be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Specimen Type
Describes the specimen type validated for testing

Tissue

Ordering Guidance

This test is not available for prenatal testing.

 

This assay is intended as a screening test to detect decreases in total pyruvate dehydrogenase complex (PDHC) activity and is used for the evaluation of patients with a clinical suspicion of a PDHC deficiency or an energy metabolism disorder. It is not designed to detect cases of pyruvate dehydrogenase (PDH) kinase or phosphatase deficiencies. Additional molecular or enzymatic testing is necessary to determine the specific defect in the PDHC; call 800-533-1710 for testing options.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Tissue in formalin or fixative preservative Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Tissue Varies

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

Pyruvate dehydrogenase complex (PDHC) deficiency is a rare mitochondrial disorder with a clinical presentation consisting of metabolic and neurological components of varying severity.

 

PDHC should be considered in patients with early-onset neurological disease and unexplained lactic acidosis, especially if structural brain abnormalities are present.

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 will always be performed at an additional charge. If viable cells are not obtained, the client will be notified.

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

The pyruvate dehydrogenase (PDH) 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 subunit, which is encoded by the PDH1 gene located on the X chromosome. Both females and males with a PDH1 gene mutation are affected with PDHC deficiency; thus, it is classified as X-linked dominant. Mutations in the PDH1 gene are typically de novo.

 

A major cause of primary lactic acidosis in children is PDHC deficiency; therefore, it should be suspected when blood and cerebrospinal fluid (CSF) lactate and pyruvate is elevated and the lactate-to-pyruvate (L:P) ratio is normal or slightly elevated. Plasma or CSF alanine (AAQP / Amino Acids, Quantitative, Plasma or AACSF / Amino Acids, Quantitative, Spinal Fluid) may also be increased.

 

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

No significant cautionary statements

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

1. Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW: The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012 Jul;106(3):385-394. doi: 10.1016/j.ymgme.2011.09.032

2. Robinson BH: Lactic Acidemia: Disorders of Pyruvate Carboxylase and Pyruvate Dehydrogenase. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed October 12, 2022. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225087140

3. 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. doi: 10.1016/s0003-2697(02)00645-0.PMID:12633610

4. Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK: Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Nov;122(3):61-66. doi:10.1016/j.ymgme.2017.09.001

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Pyruvate dehydrogenase complex (PDHC) enzyme is isolated using an immunocapture (enzyme-linked immunosorbent assay) method followed by colorimetric measurement of enzyme activity. Following addition of substrate to the isolated enzyme, PDHC activity is monitored colorimetrically and results are calculated based on the reduction of nicotinamide adenine dinucleotide (NAD[+]) to NADH.(Instruction manual: Pyruvate Dehydrogenase [PDH] Enzyme Activity Microplate Assay Kit. Abcam, Inc; 2012; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

60 to 70 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

6 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

84311-PDHC

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PDHC Pyruvate Dehydrogenase Comp, Fibro 74577-8
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
30031 Interpretation (PDHC) 59462-2
30033 Reviewed By 18771-6
38064 PDHC 74577-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports