MLYCD Gene, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Malonyl-coenzyme A decarboxylase (MCD) deficiency is a rare autosomal recessive inborn error of fatty acid metabolism characterized by reduced activity of mitochondrial malonyl-CoA decarboxylase. This enzyme is responsible for conversion of intramitochondrial malonyl-CoA to acetyl-CoA and carbon dioxide. This leads to an accumulation of malonyl-CoA, which is a strong inhibitor of carnitine palmitoyltransferase-I (CPT-I), an enzyme active in beta-oxidation of fatty acids. The resulting effect is impairment of the breakdown of fatty acids. Isoforms of CPT-I have been found in skeletal and heart muscle, liver, and brain, and symptoms seem to correlate with the localization of these isoforms. The phenotype associated with MCD deficiency is variable, but may include developmental delay, seizures, hypotonia, metabolic acidosis, hypoglycemia, ketosis, and cardiomyopathy.
The diagnosis of MCD deficiency is based on the findings of high urinary excretion of malonic acid and a mild increase in dicarboxylic acid. Acylcarnitine analysis by tandem mass spectrometry shows high blood levels of malonylcarnitine, which can be detected by neonatal screening before the appearance of symptoms. Determination of MCD activity in cultured fibroblasts can confirm the diagnosis, although this testing is not currently clinically available in the United States.
Mutations in the MLYCD gene are responsible for MCD deficiency. The MLYCD gene is located on chromosome 16 and has 5 coding exons. Several different mutations have been described including missense, nonsense, small insertions and deletions, as well as large genomic deletions.
Diagnostic confirmation of malonlyl-coenzyme A decarboxylase deficiency when familial mutations have been previously identified
Carrier screening of at-risk individuals when a mutation in the MLYCD gene has been identified in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order MCDMS/89830 MLYCD Gene, Full Gene Analysis.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical and biochemical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Salomons GS, Jakobs C, Landegge Pope L, et al: Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency. J Inherit Metab Dis 2007;30:23-28
2. Wightman PJ, Santer R, Ribes A, et al: MLYCD mutation analysis: evidence for protein mistargeting as a cause of MLYCD deficiency. Hum Mutat 2003;22:288-300