Pyruvate Dehydrogenase Complex (PDHC), Fibroblasts
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.
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