||Metabolic myopathies are genetic disorders of energy metabolism due to defects in the pathways of carbohydrate and fatty acid catabolism, and the subsequent energy production through mitochondrial oxidative phosphorylation. Mutations in genes involved in three major pathways of energy metabolism, including glycogenolysis, fatty acid oxidation, and mitochondrial oxidative phosphorylation are the main causes of metabolic myopathies. These groups of diseases are clinically heterogeneous with variable penetrance, severity and age of onset. The predominant clinical symptoms associated with metabolic myopathy include chronic muscle weakness, myoglobinuria, and/or acute and recurrent episodes of irreversible muscle dysfunction related to exercise intolerance. Patients with metabolic myopathy are usually diagnosed based on their clinical features, abnormal metabolites, and enzymatic deficiency. However, the biochemical and molecular analytical procedures are time-consuming, costly, and often not confirmatory. Definitive diagnosis is made through the identification of deleterious mutations in the causative gene. Early diagnosis of these conditions is important for prompt clinical management and improved outcome of the patients.
Twenty-six nuclear genes involved in energy metabolism are analyzed by the newly developed and clinically validated approach of Massively Parallel Sequencing (MPS) using Next Generation Sequence (NGS) technology. The genes analyzed by this panel are tabulated below . Sanger sequencing of these genes is also available using the associated individual test codes.
ACADL (#3385), ACADM (#3115), ACADVL (#3355), ACAD9 (#3900), AGL (#3670), C10orf2 (#3175), CPT1B (#3370), CPT2 (#3160), GAA (#3400), GYS1 (#3835), HADHA (#3120), HADHB (#3630), LPIN1 (#3280), OPA1 (#3465), OPA3 (#3525), PFKM (#3820), PGAM2 (#3805), PGM1 (#2520), PHKA1 (#3985), POLG (#3065), POLG2 (#3380), PYGM (#3800), RRM2B (#3420), SUCLA2 (#3375), TK2 (#3070), TYMP (#3060)
All coding exons of these 26 nuclear genes and at least 20 base pairs of flanking intronic sequences are analyzed. All exonic variants and intronic variants within 20 bp of the exon/intron boundary will be reported. Sequence analysis will not detect genomic structural rearrangements (e.g. heterozygous deletions, duplications, and inversions), large heterozygous insertion mutations (e.g. ALU mediated insertion), and mutations within the promoter or deep intronic regions. Mutations and novel variants detected by NGS are confirmed by Sanger sequencing.
Mitomet deletion/duplication analysis (#2000) for the genes covered by this panel is also available.