CPT® Code 81440

Nuclear encoded mitochondrial genes (eg, neurologic or myopathic phenotypes), genomic sequence panel, must include analysis of at least 100 genes, including BCS1L, C10orf2, COQ2, COX10, DGUOK, MPV17, OPA1, PDSS2, POLG, POLG2, RRM2B, SCO1, SCO2, SLC25A4, SUCLA2, SUCLG1, TAZ, TK2, and TYMP

Molecular genetic testing, specifically CPT® Code 81440, is utilized to identify disorders associated with nuclear encoded mitochondrial genes that predominantly present with symptoms affecting the central nervous system (CNS) and skeletal muscles. These inherited mitochondrial diseases can manifest at any age and may exhibit a range of symptoms affecting the neuromuscular system, cardiovascular system, and endocrine functions, with varying degrees of severity. The nuclear genes in question are responsible for encoding numerous proteins that play critical roles in mitochondrial oxidative phosphorylation (OXPHOS). This includes various subunits of the respiratory chain complex, proteins essential for the assembly and maintenance of the OXPHOS complex, and those involved in the replication, transcription, translation, and repair of mitochondrial DNA (mtDNA). Additionally, these genes encode proteins that are vital for mitochondrial protein synthesis and dynamics. Disorders linked to mutations in nuclear DNA (nDNA) can lead to a variety of conditions, such as Leigh syndrome and paraganglioma, which are associated with OXPHOS dysfunctions. Other examples include progressive external ophthalmoplegia (PEG) and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), which arise from defects in nDNA-encoded mitochondrial proteins that maintain mtDNA integrity. Furthermore, conditions like Friedreich ataxia and hereditary spastic paraplegia are also related to mitochondrial disorders that adversely affect the OXPHOS system. The testing process involves analyzing whole blood samples through massively parallel sequencing techniques. The CPT® Code 81440 specifically denotes the genomic sequence panel analysis that encompasses at least 100 genes, including notable ones such as BCS1L, C10orf2, COQ2, COX10, DGUOK, MPV17, OPA1, PDSS2, POLG, POLG2, RRM2B, SCO1, SCO2, SLC25A4, SUCLA2, SUCLG1, TAZ, TK2, and TYMP.