Overview of Medium-Chain Acyl-CoA Dehydrogenase Deficiency

This rare inherited metabolic disorder can be fatal if untreated

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Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD or MCAD deficiency) is a rare inherited metabolic condition that affects the body's ability to convert a certain type of fat into energy. Today, testing for MCADD is part of standard newborn screenings in many places. When diagnosed promptly, the condition can be managed. However, delays in diagnosis can be fatal.

MCAD Symptoms
Illustration by Brianna Gilmartin, Verywell

Symptoms

The body uses several types of fat for energy. The body's ability to draw on fat stores for energy is especially useful during periods of not eating (fasting) or when the body is under stress, such as when illness occurs. People with MCADD have a genetic mutation that doesn't let their bodies convert a certain type of fat—medium-chain fatty acids—into energy.

The body would typically try to use medium-chain fatty acids during periods of fasting. The symptoms of MCADD often show up after someone has gone too long without eating. In newborns, the symptoms may be kept at bay while on regular feeding schedules. However, once they start going longer stretches between feedings, or if they experience difficulty with breastfeeding, the symptoms of MCADD may emerge.

The first incidence of symptoms of MCADD typically occurs between the ages of 3 to 24 months.

MCADD symptoms can be very serious, and even fatal. Some researchers believe that undiagnosed MCADD has caused a large number of unexplained infant deaths over the last few decades. Others have proposed it may be a condition that contributes to the incidence of Sudden Infant Death Syndrome (SIDS).

The symptoms of MCADD typically show up after periods of fasting or illness, especially illnesses that cause vomiting. Symptoms can include:

  • vomiting.
  • low energy (lethargy) or being overly sleepy (somnolent).
  • weakness or low muscle tone (hypotonia).
  • low blood sugar (hypoglycemia).
  • trouble breathing or fast breathing (tachypnea).
  • liver abnormalities (enlargement, high liver enzymes).
  • seizures.

The symptoms of MCADD can be very serious. If untreated, complications can result in brain damage, coma, and death. In some cases, an infant's sudden and unexplained death is the only symptom of MCADD. Only later may it be found that the death is related to undiagnosed MCADD.

While the first symptoms of MCADD usually present in babies or early childhood, there have been cases where people did not have symptoms until adulthood. As is true for infants and children, these cases were usually precipitated by illness or fasting.

When not experiencing an acute metabolic crisis related to illness or fasting, people with MCADD usually do not have any symptoms (asymptomatic).

Causes

MCADD occurs because a person's body is unable to break down medium-chain fatty acids and convert them into energy. This is because their body doesn't produce the enzyme needed to perform this function, called medium-chain acyl-CoA dehydrogenase (ACADM). Mutations in the ACADM gene, which are present from conception, means that the body will not have enough of the enzyme to metabolize medium-chain fatty acids as a source of energy.

If a person with MCADD is supplying their body with adequate energy (through what and when they eat), they may not experience symptoms as their body will not be trying to draw on fat stores.

If a person goes without eating or gets sick, his or her body may fail to convert fatty acids into energy—this is when the symptoms of MCADD will occur. Symptoms can also develop when there is a buildup of poorly metabolized fatty acids in the body's tissues, especially in the liver and brain.

When two people who each have a mutated gene (people called "carriers") have a child together, the gene can be passed on. If a child only inherits one mutated gene, she will become a carrier like her parents. Carriers most often do not have symptoms of the condition, but they can pass the mutation on. It's also possible that a child won't inherit the mutated gene at all. However, when a child gets a mutated gene from both parents, she will develop MCADD. This is what is known as an autosomal recessive inheritance pattern.

As is often the case with genetic conditions, there are a number of possible mutations that can result in MCADD. However, researchers aren't sure if there is a specific relationship between the mutation a person has and how MCADD develops—this is also known as a genotype-phenotype relationship.

Testing for the mutations known to lead to MCADD is an important part of making the diagnosis, though it may or may not be useful in predicting the severity of a person's symptoms.

Diagnosis

MCADD is a rare condition. In the United States, it affects approximately one in 17,000 people. White people of northern European ancestry seem to have a higher risk of MCADD than other races. The condition is most common in infants or very young children, though it has been diagnosed in adults. Males and females seem to be affected at equal rates.

Testing for MCADD is now part of standard newborn screenings in many parts of the world. However, it is not routinely tested for at every hospital. Therefore, if an infant or young child begins to show symptoms that are indicative of the condition, prompt testing, diagnosis, and treatment are very important.

Left untreated, the condition can cause serious complications, including sudden death.

The primary benefit of including testing for MCADD in newborn screenings is that an infant can be diagnosed before symptoms develop. This reduces the chance that the condition will go undiagnosed and untreated, which can have serious (if not fatal) consequences.

If an infant's newborn screening indicates they could have MCADD, additional testing can provide more information. Parents of a child diagnosed with MCADD may also be tested, as well as the child's siblings.

Other tests that may be used to confirm a diagnosis of MCADD include:

  • genetic testing to look for mutations in the ACADM gene.
  • blood tests to measure glucose, ammonia, and other levels.
  • urine tests to rule out other conditions that cause low blood sugar.

When symptoms of MCADD are present and a person is in an acute metabolic crisis, they may also need other medical interventions. This may include replenishing electrolytes with intravenous (IV) fluids or supplemental nutrition.

If a person doesn't experience symptoms until adulthood, MCADD may not be the first diagnosis a medical professional suspects. After considering the person's medical history (including family history), current symptoms, what the person was doing before they got sick (such as if he had a viral illness that caused vomiting or has been fasting), together with any lab results, MCADD may be tested for.

In some cases, particularly in young children, MCADD is confused with another condition known as Reye Syndrome.

While the two conditions may have similar symptoms and can both develop after a period of illness (especially childhood illnesses like chicken pox) Reye Syndrome occurs in children who were treated with aspirin during their bout of sickness. While Reye Syndrome has been specifically linked to aspirin use in children, MCADD is not associated with the use of any specific medication.

Treatment

The primary way to treat MCADD is to prevent the symptoms of the condition from developing, as they can be quite serious. Parents of a newborn diagnosed with MCADD will be given strict instructions about feeding to prevent any long periods of fasting.

In addition to making sure they do not go too long without eating, people with MCADD usually need to adhere to a specific diet that includes higher amounts of carbohydrates and lower amounts of fat than may be typically recommended. If a person becomes ill and cannot eat, she usually needs to receive nutrition and fluids through an IV or tube (enteral) at the hospital to prevent MCADD symptoms and complications from developing.

Newborns with MCADD who struggle to breastfeed may be more likely to enter a state of metabolic decompensation, as they are not able to keep their metabolic needs consistent through the nutrition they take in. In addition to having regular bottle feedings, some doctors may recommend infants be given mixtures of simple carbohydrates (such as uncooked cornstarch) to help prevent MCADD symptoms from developing.

In addition to ensuring the diet is adequate in nutrition, strict adherence to a regular feeding schedule will need to begin from the time a child with MCADD is born or from the time they are diagnosed. For infants, this usually means going no longer than four to five hours between feedings. Older children and adults should avoid fasting for longer than 10 hours and no person with MCADD, regardless of age, should fast for longer than 12 hours. If longer periods of fasting are required, such as for a medical test, close medical management will be necessary.

In the past, supplemental carnitine (a compound that helps cells produce energy) was investigated as a potential management strategy for MCADD, but the research exploring its benefit is not conclusive.

Additionally, when a person with MCADD becomes ill, especially if they are vomiting, they may need to seek medical attention to prevent MCADD-related symptoms and complications from developing.

Children with MCADD may need to wear a medical alert bracelet. Parents may also have their pediatrician send a letter to a child's school and teachers to let them know about the child's condition and outline the importance of adhering to dietary needs and eating schedules.

Any person who is interacting with a child who has MCADD should be aware of the symptoms as well as the situations that can precipitate them—someone around a child with MCADD should know what to do if a metabolic crisis is suspected.

As long as a person with MCADD adheres to what is required to manage the condition, they can usually lead otherwise healthy lives. However, it is not uncommon for the diagnosis of MCADD to be made after death; the first onset of symptoms, and the metabolic crisis that results can progress rapidly. Therefore, early diagnosis and treatment remain crucial to the long-term outlook for a person with MCADD.

A Word From Verywell

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD or MCAD deficiency) is a rare inherited metabolic condition that affects the body's ability to convert a certain type of fat into energy. If the condition goes undiagnosed and untreated, it can be fatal. Many newborn screenings include testing for MCADD, but they are not yet universally present. If a doctor suspects an infant has MCADD, genetic testing will be needed. People with MCADD usually need to adhere to a diet that is high in carbohydrates and low in fat. They also need to ensure they do not go long periods without eating (fasting). Children with MCADD may need to wear a medical alert bracelet to make sure those around them can recognize the symptoms of a metabolic crisis. While the consequences of untreated or poorly managed MCADD can be devastating, when the condition is accurately diagnosed and a treatment plan is in place, most people with MCADD can lead otherwise healthy lives.

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