Guidance

Isovaleric acidaemia (IVA): detailed information

Updated 18 November 2021

Applies to England

Public Health England (PHE) created this information on behalf of the NHS. In it, the word ‘we’ refers to the NHS service that provides screening.

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This information is for parents if their baby is suspected of having IVA or has been diagnosed with IVA following their newborn blood spot screening test (‘heel prick test’). It will help you and your healthcare professionals to talk through the next stages of your baby’s care.

About IVA

Isovaleric acidaemia (pronounced iso-val-air-ik acid-ee-mia), or IVA, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. Babies with IVA inherit 2 faulty copies of the gene for IVA, one from each parent.

When we eat, our body breaks down protein in food into smaller parts called amino acids. Enzymes, which are chemicals found naturally in our body, then break down the amino acids further so they can be used.

In IVA, an enzyme called isovaleryl-CoA dehydrogenase is missing, which leads to problems breaking down the amino acid leucine. This causes a harmful substance called isovaleric acid to build up in the body.

Untreated IVA can cause long-term health problems, including brain damage, but with newborn screening and early treatment this can be prevented.

Screening and diagnosis of IVA

Newborn blood spot (‘heel prick test’)

When your baby was about 5 days old, your midwife took some blood from your baby’s heel for their newborn blood spot screening test (the ‘heel prick test’). The newborn blood spot screening test measures the amount of a substance called C5-acylcarnitine in the blood. A high level of C5-acylcarnitine suggests your baby may have IVA. This is called a screen positive result.

Diagnostic tests

If your baby has a screen positive result, you will be seen by a metabolic doctor, dietitian and nurse specialist (the ‘metabolic team’). The team will provide advice and support. Blood and urine tests will be carried out to confirm if your baby has IVA.

You will need to wait a few days for the test results to be reported. During this time, you can continue to breastfeed or give normal infant formula. You should feed your baby every 3 to 4 hours, day and night, or more often if demanded. If your baby becomes unwell, you should take them to hospital for further assessment.

Some babies may already be unwell and on treatment before the screening test results are reported.

Treatment

If your baby does have IVA, the metabolic team will:

• explain the condition in detail and answer any questions you might have
• start your baby on medical treatment and a special diet, which includes:
• medicines called L-carnitine and/or glycine, which help to reduce the level of isovaleric acid in the blood
• a restricted protein feeding plan
• a special feed to use during illnesses (called the emergency regimen)
• provide you with written information and contact details for the metabolic team
• arrange regular follow-up appointments

The metabolic team will see you regularly throughout your child’s life and your child will remain under their care.

The restricted protein feeding plan

The aim of the feeding plan is to limit your baby’s protein intake in order to reduce the harmful build-up of isovaleric acid in the body.

Your baby will be given 2 different feeds to provide all the nutrition they need for growth and development. These are:

• a limited daily volume of breastmilk feeds or infant formula
• a protein-free infant formula

Your metabolic dietitian will teach you how much of each feed to give based on your baby’s weight. Following the dietetic instructions is very important for your baby’s health.

Your GP will be asked to prescribe the protein-free infant formula. You will continue to have regular appointments with a metabolic dietitian who will advise on dietary management throughout the various stages of childhood.

What to do if your baby gets ill

If your baby becomes ill, they might have an episode known as a metabolic crisis (also known as metabolic decompensation). This is caused by a rapid build-up of isovaleric acid and other related substances in their body, which can make them severely unwell.

Symptoms of a metabolic crisis include:

• irritability
• sleepiness and non-responsiveness
• floppiness and falling over
• poor feeding
• breathing difficulties
• seizures
• coma

A metabolic crisis can lead to serious illness and long-term brain damage, and can be life-threatening.

To help prevent this from happening, you will be taught to give an emergency regimen, which involves specialist feeds and frequent feeding. If your baby becomes very unwell, they might need to be admitted to hospital.

The metabolic team will teach you how to look after your child during illness.

The emergency regimen

The emergency regimen is made up of glucose polymer feeds and L-carnitine and/or glycine medicines. It is given regularly, day and night, to provide energy and help limit the build-up of harmful substances in the body.

You should start the emergency regimen if your baby becomes unwell or is not tolerating their usual feeds. Your metabolic dietitian will teach you:

• how to prepare the emergency feed
• how much feed to give your baby
• how often you should feed your baby

Your GP will be asked to prescribe the glucose polymer powder.

The emergency regimen guidelines are available from the British Inherited Metabolic Diseases Group (BIMDG) website.

You should contact the metabolic team at the start of any illness to let them know your baby is unwell and that you have started the emergency regimen.

Signs of illness may include:

• fever
• vomiting
• cough/cold
• sore throat
• chest infection
• diarrhoea
• not being their usual self

You should take your baby to hospital immediately for further assessment if they do not tolerate the emergency regimen or their symptoms are getting worse.

You should take with you any information you have been given about IVA, including your:

• emergency regimen instructions
• BIMDG guidelines
• L-carnitine and/or glycine
• glucose polymer powder and scoops

Long-term outlook

With treatment, the outcome is usually very good and most children with IVA will avoid any long-term health problems.

Your other children

At-risk siblings

Children from the same parents have a 1 in 4 chance of having IVA. Your other children might be at risk of IVA even if they have never shown any symptoms. It is therefore very important to get them tested if they have not been previously screened for IVA. Your metabolic team will be able to arrange this testing.

Future children

A new baby from the same parents will also have a 1 in 4 chance of having IVA. When you find out that you are pregnant, you should tell your midwife and GP there is a family history of IVA. You should also inform your metabolic team early in the pregnancy.

The metabolic team will write a birth plan for you. This will include advice on an early screening test for your new baby which should be taken between 24 and 48 hours after birth. This blood test will be in addition to the routine newborn blood spot screening test. The birth plan will be given to you and shared with your obstetrician and local midwifery team.

You should notify your metabolic team once you have given birth so they can ensure the correct blood tests are taken and sent to the screening laboratory without delay.

Confidentiality

The NHS screening programmes use personal information from your NHS records to invite you for screening at the right time. Public Health England also uses your information to ensure you receive high quality care and to improve the screening programmes. Find out more about how your information is used and protected, and your options.

More information and support

The metabolic team will be happy to discuss any queries you might have.

Further information can be found at Metabolic Support UK. The Metabolic Support UK team can be contacted at:

• 0845 241 2173 or 0800 652 3181
• contact@metabolicsupportuk.org

The BIMDG website has the emergency regimen guidelines and a TEMPLE booklet about IVA.

NHS.UK has information about IVA and newborn blood spot screening.