Pyruvate Dehydrogenase Complex (PDHC), Fibroblasts
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 test or proper submission of the test request
This assay is intended to detect decreases in total activity as a whole; it is not designed to detect cases of PDH kinase or phosphatase deficiencies.
Additional Tests Lists test(s) that are always performed, at an additional charge, with the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|CRYOB||Cryopreserve for Biochem Studies||No||Yes|
Testing Algorithm Delineates situation(s) 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 10 days, client will be notified.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
PDHC/83899: Radioisotopic Enzyme Assay
FIBR/8482: Cultivated from Biopsy as Monolayer
CRYOB/88832: Fibroblast Subculture Followed by Cryopreservation and Storage
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Pyruvate Dehydrogenase Comp, Fibro
PDC (Pyruvate Dehydrogenase Complex)
PDHC (Pyruvate Dehydrogenase Complex)
PDHC (Pyruvate Dehydrogenase Complex)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test is not recommended for prenatal testing.
1. 1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. 2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
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
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 [Supply T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen in formalin or fixative preservative
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
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, which is an entry point for the tricarboxylic acid (TCA) cycle and 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. Seizures and ataxia are also frequent features. Less common manifestations include congenital brain malformations, particularly agenesis of the corpus callosum, or degenerative changes, including Leigh disease. Facial dysmorphism can be seen as well. The severity of the disease progression is thought to be related to the severity of the lactic acidosis.
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. It is considered an X-linked dominant condition in that both females and males with an E1 alpha gene mutation are affected with PDHC deficiency. 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/9265 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.
Range: 1.63-3.61 mU/mg protein
Range: 0.18-2.18 mU/mg protein
Reference values apply to all ages.
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 activity as a whole; it is not designed to detect cases of pyruvate dehydrogenase kinase or phosphatase deficiencies.
Clinical Reference Provides recommendations for further 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 Gen Met 2012;106:385-394
2. Robinson BH: Lactic acidemia: disorders of pyruvate carboxylase and pyruvate dehydrogenase. In The Online Metabolic and Molecular Basis of Inherited Disease. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. Available from URL: http://dx.doi.org/10.1036/ommbid.128 Retrieved 6/25/12
Method Description Describes how the test is performed and provides a method-specific reference
Pyruvate dehydrogenase complex (PDHC) activity is determined by measuring the (14)CO(2), the end product of the E1 component of PDHC from (1-C) pyruvate. In skin fibroblasts, 90% to 95% of PDHC activity is inactivated. The enzyme is activated by pretreating fibroblast cells with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase.(Sheu KF, Hu CW, Utter MF: Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts. J Clin Invest 1981 May;67:1463-1471)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
60-70 days depending on rapidity of growth
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
3 years - Check with the lab for availability
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
88240-Cryopreservation for biochemical studies
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|30027||Reason For Referral||42349-1|
|30029||PDHC, Activated||In Process|
|30030||PDHC, Inactivated||In Process|