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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

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.

 

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 pyruvate dehydrogenase complex 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 pyruvate dehydrogenase complex. Call 800-533-1710 for test options.

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 (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, 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. 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

5. Shin HK, Grahame G, McCandless SE, et 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

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