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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|