Specimen Requirements

Alternate Specimen Requirements

Minimum Specimen Requirements

Stability

Days Performed

Varies

Turnaround Time

9 - 16 days

Methodology

Reference Range

Special Info

Useful as a circulating biomarker in myopathy-related mitochondrial disease as well as other conditions.

Clinical Info

Mitochondria perform many important metabolic functions, the most vital being the production of energy in the form of adenosine triphosphate (ATP) through the electron-transport chain and the oxidative phosphorylation system, which consists of 5 complexes (Complex I-V). Each of these complexes consists of between 4 and 46 subunits encoded by both nuclear and mitochondrial DNA. Mitochondrial diseases are caused by defects in any of the relevant metabolic pathways and have an estimated prevalence of 1:8,500. Mitochondrial diseases are varied, including mitochondrial DNA deletion syndromes such as Kearns-Sayre syndrome (KSS), mitochondrial depletion syndromes such as those caused by mutations in TK2 and SUCLA2 or POLG and C10orf2, and mitochondrial point mutation syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), as well as others. The clinical features of mitochondrial diseases vary widely, but they can include lactic acidosis, myopathy, ophthalmoplegia, ptosis, cardiomyopathy, sensorineural hearing loss, optic atrophy, pigmentary retinopathy, diabetes mellitus, encephalomyopathy, seizures, and stroke-like episodes. A diagnostic workup for a mitochondrial disorder may demonstrate elevations of the lactate-to-pyruvate ratio (LAA / Lactate, Plasma and PYR / Pyruvic Acid, Blood) and an elevated growth differentiation factor 15 (GDF15) level. GDF15 is a protein of the transforming growth factor beta superfamily. GDF15 is overexpressed in muscle and serum in patients with various types of mitochondrial diseases, including those with mitochondrial deletion, depletion, and point mutation syndromes. Therefore, increased levels of GDF15 can indicate the need for further investigations including molecular studies and muscle biopsy to confirm the presence of a possible neuromuscular mitochondrial disease. This is a screening test for neuromuscular mitochondrial disease. Results can be elevated for other reasons including in individuals with cancer, cardiovascular disease, diabetes, and pregnancy. Results are normally elevated in children younger than 3 months of age due to the high levels found in the placenta during pregnancy. This assay is not suitable for carrier detection. References: 1. DiMauro S and Schon EA: Mechanisms of Disease: Mitochondrial Respiratory-Chain Diseases. N Engl J Med 2003;348:2656-2668 2. Kalko SG, Paco S, Jou C, et al: Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies. BMC Genomics 2014;15:91 3. Sugulle M, Dechend R, Herse F et al: Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus. Hypertension 2009 Jul;54(1):106-112