The Invitae Elevated C3-DC Test analyzes the MLYCD gene, which is associated with elevations of C3-DC acylcarnitine on newborn screening (NBS) or plasma acylcarnitine analysis. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions.
The Invitae Organic Acidemias Panel has been designed to provide a broad genetic analysis of this class of disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.
Elevated C3-DC acylcarnitine may be detected during newborn screening (NBS) or acylcarnitine analysis due to malonyl-coA decarboxylase deficiency. Patients with this disorder show variable phenotypic expression and may present in the neonatal period or with a later onset. Patients with the severe form have been reported with developmental delay, recurrent hypoglycemia, malonic aciduria, lactic acidosis, ketosis, hyperammonemia, seizures, and cardiomyopathy, all of which have variable presentation. Patients with later-onset disease may present with intermittent metabolic crises during times of intercurrent infections. Developmental delay, speech delay, and cardiomyopathy may also be present. A low-fat, high-carbohydrate diet with MCT-oil and carnitine supplementation has been used to treat patients; this diet has had some success in the treatment of cardiomyopathy, a life-threatening complication of this disorder. Early diagnosis and detection may improve the long-term outcome of these patients.
For patients with biochemical features that are consistent with malonic aciduria (elevated C3-DC on acylcarnitines and elevated urine malonic acid), approximately 90% will have two pathogenic variants in MLYCD.
Malonyl-coA decarboxylase deficiency is inherited in an autosomal recessive manner.
The prevalence of elevated C3-DC is dependent on laboratory cutoffs and ethnicity. The overall prevalence of confirmed Malonyl-coA decarboxylase deficiency has been estimated at <1 in 300,000.
This test may be appropriate for patients:
For considerations for testing please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|