Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder that affects the breakdown of fatty acids for energy. It is classified as a fatty acid oxidation disorder. MCADD specifically involves a deficiency of the enzyme medium-chain acyl-CoA dehydrogenase, which is essential for the normal processing certain fatty acids. The prevalence of MCADD in the general population is approximately 5 per 100,000 births and may vary according to the population. It is especially prevalent in people from Northern Europe.
Medium-chain acyl-CoA dehydrogenase deficiency genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Medium-Chain Acyl-CoA Dehydrogenase Deficiency include:
- Impaired Fatty Acid Oxidation: Individuals with MCADD have a reduced ability to break down medium-chain fatty acids into energy, leading to an energy deficiency.
- Episodic Symptoms: Symptoms of MCADD often occur during periods of fasting or increased energy demands, such as during illness or prolonged periods without food.
- Hypoglycemia: The impaired breakdown of fatty acids can result in low blood sugar levels (hypoglycemia), leading to symptoms such as weakness, lethargy, and seizures.
- Hepatomegaly: Enlargement of the liver (hepatomegaly) may occur during episodes of metabolic stress.
- Vomiting and Hypotonia: Infants with MCADD may experience vomiting, poor feeding, and hypotonia (weak muscle tone).
- Episodic Encephalopathy: Severe metabolic stress can lead to encephalopathy, a condition characterized by neurological symptoms such as confusion, seizures, and a decreased level of consciousness.
- Maple Syrup Odor: In some cases, individuals with MCADD may have a distinctive odor in their sweat or urine, resembling maple syrup.
MCADD is caused by ACADM gene mutations, which provide instructions for making the medium-chain acyl-CoA dehydrogenase enzyme.
Management of MCADD involves dietary interventions and vigilant monitoring to prevent metabolic decompensation during fasting or illness. Treatment may include:
- Regular Feeding: Individuals with MCADD are encouraged to eat regular meals and snacks to prevent prolonged periods without food.
- Avoidance of Fasting: Fasting, especially during illness, can trigger metabolic crises in individuals with MCADD. Therefore, it is essential to avoid prolonged fasting.
- Emergency Plan: A well-defined emergency plan is often established for individuals with MCADD to guide medical management during episodes of metabolic decompensation.
- Dietary Modifications: In some cases, dietary modifications may involve avoiding certain fatty acids, and supplementation with medium-chain triglycerides may be considered.
Early diagnosis through newborn screening allows for early intervention and prevention of metabolic crises. Genetic counseling is essential for affected individuals and their families to understand the inheritance pattern and assess the risk of having affected children.
More Information
The ACADM gene encodes for medium-chain acyl-CoA dehydrogenase, an enzyme involved in the initial step of mitochondrial beta-oxidation of fatty acids. This is an aerobic process that breaks fatty acids into acetyl-CoA, from which energy is obtained.
Several pathogenic variants have been identified in ACADM that cause the disease. Of these, the c.985A>G variant is the most frequent in northern Europeans in 80% of patients. This variant produces an amino acid change that affects the correct functionality of the protein.
Another frequent pathogenic variant in MCADD patients is c.199T>C, with an allelic frequency of approximately 6%. The presence of this variant in compound heterozygosis together with c.985A>G is usual. Patients compound heterozygous for c.985A>G and c.199T>C usually show milder clinical manifestations, whereas those homozygous for c.985A>G show symptoms after birth.
Medium-chain acyl-CoA dehydrogenase deficiency genetic testing analyzes the 18 most frequent pathogenic mutations of the ACADM gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
