Evaluation of patients with a clinical suspicion of a pyruvate
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.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
FIBR | Fibroblast Culture | Yes | Yes |
CRYOB | Cryopreserve for Biochem Studies | No | Yes |
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.
PDHC: Colorimetric Enzyme Assay
CRYOB: Fibroblast Subculture followed by Cryopreservation and Storage
PDC (Pyruvate Dehydrogenase Complex)
PDHC (Pyruvate Dehydrogenase Complex)
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.
Tissue
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.
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
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 in Special Instructions:
-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.
Tissue in formalin or fixative preservative | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Tissue | Varies (preferred) |
Evaluation of patients with a clinical suspicion of a pyruvate
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.
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.
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.
>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.
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.
No significant cautionary statements
1. Patel KP, Obrien TW, Subramony SH, Shuster J, Stacpoole PWet al: The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012;106:385-394. doi: 10.1016/j.ymgme.2011.09.032.
2. Robinson BH:. Lactic Aacidemia: Disorders of Ppyruvate Ccarboxylase and Ppyruvate Ddehydrogenase. 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 June 03, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225087140 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. 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. doi: 10.1016/s0003-2697(02)00645-0.PMID:12633610
5. Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JKet al: Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017;122(3):61-66 doi:10.1016/j.ymgme.2017.09.001
Pyruvate dehydrogenase complex (PDHC) enzyme is isolated using an immunocapture (enzyme-linked immunosorbent assay: ELISA) 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)
Varies
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.
84311-PDHC
88233-Fibroblast culture
88240-Cryopreservation for biochemical studies
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 |