MLYCD Gene, Full Gene Analysis
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 (C3DC), 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.
Confirmation of diagnosis of malonyl-CoA decarboxylase deficiency
Carrier screening in cases where there is a family history of malonyl-CoA decarboxylase deficiency, but disease-causing mutations have not been identified in an affected individual
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
A small percentage of individuals who are carriers or have a diagnosis of malonyl-CoA decarboxylase (MCD) deficiency may have a mutation that is not identified by this method (eg, promoter and deep intronic mutations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of MCD deficiency. For carrier testing, it is important to first document the presence of a MLYCD gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
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.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
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