Causes of MCADD
Causes of MCADD (Medium-chain acyl-CoA dehydrogenase deficiency) are rooted in genetic mutations that impair the body’s ability to metabolise certain fats for energy, particularly during periods of fasting or illness.
This rare condition happens because the body lacks a working enzyme that normally breaks down specific types of fat. These fats, called medium-chain fatty acids, are a key energy source when glucose runs low. When this enzyme doesn’t work, the body can’t turn these fats into fuel. As a result, energy levels drop quickly, especially during illness or long gaps between meals.
The Role of the ACADM Gene
The causes of MCADD can be traced to a faulty ACADM gene. This gene gives the body instructions to make the medium-chain acyl-CoA dehydrogenase enzyme. The enzyme works in the mitochondria, which are tiny energy-making parts inside cells.
When the ACADM gene has mutations, the body either makes a broken enzyme or none at all. Without this enzyme, medium-chain fatty acids build up and can’t be used for energy. This is especially dangerous when glucose levels drop, like during an illness or skipped meals.
MCADD becomes most dangerous when the body needs extra energy—during infections, after vomiting, or while fasting. In these moments, the body tries to burn fat for fuel. But in MCADD, that process fails, leading to a sudden energy crisis.
Inheritance and Genetic Patterns
The causes of MCADD are inherited in an autosomal recessive pattern. This means both parents must carry one copy of the faulty gene for a child to be affected.
Carriers usually have no symptoms. But if both parents carry the gene, there’s a 25% chance their child will have MCADD. That’s why family history and carrier testing are so important, especially in certain populations where MCADD is more common.
The most well-known gene mutation that causes MCADD is called c.985A>G. It shows up often in people of Northern European descent. This version leads to a complete or near-complete loss of enzyme function.
Some people carry other, less common mutations. These may cause milder forms of MCADD or show symptoms only later in life. These mild cases can be harder to detect without genetic testing.
Environmental Triggers and Metabolic Stress
While genetics explain the root cause, certain situations trigger MCADD symptoms. The biggest one is fasting. In healthy people, fasting leads to fat burning. But in children with MCADD, that process doesn’t work.
Instead of making energy from fat, their bodies build up harmful substances. This causes blood sugar to drop and can lead to serious illness.
Other triggers include vomiting, poor appetite, and common infections. Even mild colds or stomach bugs can set off a crisis if the child isn’t eating well. These everyday challenges quickly become emergencies when the body can’t switch to fat metabolism.
These triggers explain why preventing long gaps between meals is one of the most important parts of MCADD care.
How Metabolism Breaks Down
The causes of MCADD also involve a deeper problem in the body’s energy pathways. Fat breakdown is a complex chain of steps. When one part—like the medium-chain enzyme—is missing, the whole system struggles.
This leads to more than just low energy. The build-up of fatty acids and other waste products puts stress on the liver and other organs. That’s why early detection and proper care can prevent serious problems.
Many countries now screen all newborns for MCADD. These tests catch the condition early—before symptoms start. With early diagnosis, families can avoid fasting and take quick action when illness hits.
Rare and Milder Presentations
Not everyone with MCADD shows symptoms early. Some people with milder mutations may not have trouble until later in life. They may get very tired, dizzy, or ill when they miss meals or exercise hard.
Others may never have symptoms at all unless they face extreme stress or illness. Still, these people are at risk if their condition goes undiagnosed. That’s why doctors should consider MCADD in anyone with unexplained low blood sugar, sudden infant death, or repeated fainting episodes.
In families where parents are related by blood (consanguineous marriages), the chances of passing down two faulty genes are higher. This makes family history even more important.
Summary of Causes of MCADD
To summarise, causes of MCADD come from inherited changes in the ACADM gene. These changes stop the body from making an enzyme needed to turn fat into energy.
While the genetic mutation is the main cause, other factors like fasting, illness, and physical stress act as dangerous triggers. When they happen, the body quickly runs out of energy and serious problems begin.
Understanding the causes of MCADD helps families, doctors, and caregivers take the right steps early. With newborn screening, education, and careful feeding, most children with MCADD can stay healthy and avoid life-threatening crises.
