Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare genetic condition where a person has problems breaking down fatty acids for energy.

This means that if they go for long periods without eating, they can experience a range of unpleasant symptoms, such as:

feeling very tired and sluggish
being sick
seizures (fits)

Left untreated, MCADD can lead to more serious complications – such as coma, brain damage and liver failure – and can sometimes be fatal.

Symptoms can be triggered once a baby has stopped receiving regular nightly feeds. There have also been cases where symptoms begin shortly after birth, due to an interruption in a newborn baby’s feeding. Symptoms may also occur when your baby is ill.

What happens in MCADD?

People with MCADD are born with a faulty or missing enzyme that the body normally uses to break down fatty acids (an enzyme is a protein that can cause a chemical reaction inside cells).

During long periods between eating, the body breaks down its fat stores to produce energy. Fats are broken down into fatty acids, which are then broken down into shorter and shorter lengths (by breaking the chains holding them together). At each step, energy is released.

When people with MCADD go for a long period of time without eating, two harmful effects occur:

there is a build-up of medium-chain fats inside the body, which can have a toxic (poisonous) effect
the body then uses its glucose resources as an alternative energy source; this can lead to a sudden and severe drop in blood sugar levels (hypoglycaemia)

The faulty or missing enzyme is the result of genetic mutations a child inherits from their parents (the parents themselves are usually unaffected by MCADD).

A genetic mutation is when the instructions found in all living cells (DNA) becomes scrambled so that one or more of the body’s processes does not work properly.

How is MCADD treated?

There is no cure for MCADD. Treatment involves making sure you don't go for long periods without eating.

The maximum "safe fasting time" for children who are not ill can vary, depending on their age.

Speak to your doctor for advice on the maximum time your child should fast for. Children who are ill need to be fed more frequently.

If your child experiences any symptoms of MCADD, there are many high-glucose drinks that can be used to boost blood sugar levels. If your child is not drinking, or does not improve quickly, hospital treated will be needed.

Screening

In the past, babies with MCADD went undiagnosed until they experienced symptoms – often known as an acute attack or metabolic crisis.

This could be life-threatening, as the parents usually had no idea what was happening or how to treat the symptoms.

Because of this, the NHS introduced a screening programme for MCADD in 2009. All newborn babies in England are given a blood test that can be used to screen for MCADD.

Who is affected

MCADD is a rare condition. It is estimated that around 1 in 8,000 babies is born with the condition. Both sexes are equally affected.

Outlook

The outlook for MCADD is usually very good, as the condition is relatively straightforward to manage. Providing that the condition is diagnosed and that dietary recommendations are met, there is no reason why a child with MCADD cannot live a normal healthy life.

Symptoms

Symptoms of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) can occur:

after not eating (fasting) for a long period
during or after an infection, such as the common cold – being ill increases the body’s demand for energy and can also cause loss of appetite

Symptoms of MCADD include:

your baby or child appearing unusually tired, sluggish and lazy
being sick
excessive sweating
rapid breathing
swelling of their liver, which may be noticeable by touch
seizures (fits)

Older children and adults may appear unusually nervous and excitable.

If left untreated, MCADD can be life-threatening. The brain can swell, causing brain damage, the liver can stop functioning (liver failure) and there’s a risk of slipping into a coma.

You will be given an emergency contact number to call immediately should your baby or child start experiencing the symptoms of MCADD.

If this information is not easily available, call 999 for an ambulance or go to your nearest accident and emergency (A&E) department and tell them your child is experiencing symptoms of MCADD.

Causes

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) occurs when an enzyme called medium-chain acyl-CoA dehydrogenase (MCAD) is either missing or does not work properly.

This is due to a fault in the gene that provides instructions for making the enzyme. If this happens, the body cannot break down stored fat to release energy.

Fats are normally broken down into fatty acids, which are then broken down into shorter and shorter lengths, with each step producing energy. If your child has MCADD, there is a build-up of medium-length chains due to a MCAD enzyme deficiency.

If the body needs to break down fats quickly (for example, if your child hasn't eaten for a while or is unwell), this build-up of medium-chain fats can become toxic, leading to serious, even life-threatening, symptoms.

In cases of MCADD, the body relies on glucose (a type of sugar in the blood) to produce energy. If someone isn’t eating properly or they are ill, their glucose may be all used up and their blood sugar levels will drop to a dangerously low level, which is known as hypoglycaemia.

The genetics of MCADD

Most cases of MCADD are caused by a genetic mutation called 985A>G. This is thought to be present in around 1 in every 125 people in Europe (the figure may be different in other parts of the world).

Genes come in pairs. You receive one copy of a gene from your mother and one copy from your father. A person needs a pair of the mutated genes to develop MCADD – one from their mother and one from their father.

Usually, a child with MCADD has parents who are unaffected by the condition, but both have a single mutated gene.

This means that the children of two parents "carrying" the 985A>G gene mutation have a 25% chance of inheriting the condition.

If you are an adult with MCADD, your children are unlikely to be affected unless you conceive a child with someone who is also a carrier of the mutation. If this happens, there is a 50% chance of your child developing MCADD.

Diagnosing

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is diagnosed either at birth, through the NHS Newborn Screening Programme or by investigating typical symptoms of MCADD.

Newborn screening

The NHS Newborn Screening Programme was introduced in 2009 to help detect and treat conditions such as MCADD, before a person suffers any life-threatening symptoms. All newborn babies in England are offered routine health checks during the first week of their life, including a blood test, which can be used to screen for MCADD.

During the screening test, the midwife takes blood from your baby's heel. The blood is then checked for abnormalities in the levels and makeup of fats in the blood, which occur when the body is unable to break down fatty acids.

The diagnosis is confirmed using a genetic test. This is done by extracting a sample of DNA from your baby’s blood and checking the genetic information stored in it for mutations known to cause MCADD, such as the 985A>G mutation.

If the diagnosis is positive, you will be referred to a specialist for further investigation.

Family history

If you and your partner have previously conceived a baby with MCADD, there is a 25% (1 in 4) chance that any children you conceive in the future will also be born with MCADD.

Because of this, it is recommended that babies born in families with a history of MCADD receive specialist monitoring and a feeding regimen until screening test results are known.

If your child is diagnosed with MCADD and they have any siblings who have not been screened before, it's important they are also tested. They may be at risk, even if they have had no symptoms.

You may be asked to bring any siblings to the hospital at the first follow-up appointment after diagnosis.

Treatment

A comprehensive plan will be drawn up for your child by a specialist with experience in treating medium-chain acyl-CoA dehydrogenase deficiency (MCADD).

The plan will cover:

how often your child should eat
what your child should eat
what you should do if your child is not eating normally due to illness or similar – this usually involves giving your child high-glucose drinks

You will be given a number of sachets, consisting of glucose and oral rehydration solutions, which can be used in an emergency.

As part of this plan, you will regularly meet with a dietician so that your child’s progress can be tracked and you can discuss any issues. A dietician is a health professional who works with people that have special dietary needs.

Other members of your child’s care team may include:

a doctor who specialises in the treatment of children (paediatrician)
health visitor
a specialist nurse

You will also be given telephone numbers you can use in case of an emergency.

Dietary advice will change as your child gets older. Speak to your care team for more information.

The only food your child should avoid eating is coconut, as it contains large amounts of fatty acids that they will be unable to digest.

What to do if your baby is unwell

If your baby becomes unwell and starts refusing feeds, you should first contact your care team for advice.

They will usually tell you to make a drink using a sachet of glucose mixed with 200ml of cooled boiled water.

If your child is also experiencing diarrhoea or being sick, you should make a similar drink consisting of 200ml of water and a combination of glucose and oral rehydration solution.

The fluid can then be poured into a bottle or cup, depending on what your baby finds easiest.

Your dietician will provide more detailed instructions and information sheets.

You should contact your care team for further advice if your baby:

is experiencing persistent diarrhoea and/or vomiting
is unable or unwilling to take the recommended fluid intake
is breastfed and will not accept fluid from a bottle or cup
has not resumed normal feeds within 48 hours

Older children

Older children should be encouraged to eat three meals a day: breakfast, lunch and dinner.

Snacks between meals are not usually recommended unless your child has a poor appetite.

If snacks are required, they should be given at regular intervals to prevent constant snacking (grazing), which could affect appetite.

It is usually safe for your child to sleep through the night without needing to be fed, as long as they eat something small before going to bed, such as milk and cereal or toast.

Your child should eat breakfast soon after waking up. If they refuse breakfast, a sugary drink (see below) can be given as an alternative, with a mid-morning snack before lunch. However, this should not be encouraged on a regular basis.

You should never let a child over the age of 1 fast for more than 12 hours.

What to do if your child is unwell

You will need to give them an emergency drink.

Alternatively, you can give them commercially available sugary drinks that contain high amounts of glucose. These include:

Fruit Shoots
J20
a carton of Ribena (the original type, not the reduced sugar or sugar-free types)
Lucozade energy (but not the sport variety, as that does not contain enough glucose)
fizzy drinks such as cola or lemonade (again, make sure they are not sugar-free or diet versions)

(Note – the use of brand names is for information purposes only. It does not imply any endorsement for these products by NHS Choices or any related organisation).

The long-term use of these types of sugary drinks is not encouraged as they can cause health problems in later life, such as tooth decay and diabetes.

Contact your care team for advice if your child refuses the fluid or is unable to keep it down.

Advice for adults with MCADD

There are a number of issues that adults with MCADD need to be aware of. These are discussed below.

Alcohol

Heavy alcohol consumption, especially binge drinking, can be dangerous if you have MCADD because:

people often pass out after binge drinking, so the time before eating your next meal could become dangerously delayed
alcohol can cause your blood sugar levels to drop, which can trigger the symptoms of MCADD

If you do choose to drink alcohol, consume in moderation and never on an empty stomach.

Weight management

If you are trying to lose weight, you should discuss the safest way to do this with your care team.

It is especially important to avoid fad or crash diets, as a sudden change in the amount and type of food that you eat could trigger symptoms.