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Isovaleric Acidaemia (IVA)
Information for Health Professionals
What is Isovaleric Acidaemia?
Version 1 December 2014
Isovaleric Acidaemia (IVA) is a rare inherited disorder that prevents the breakdown of a
building block of protein, the amino acid leucine. This then causes a harmful build up of a
substance called isovaleric acid in the blood. Without treatment IVA can lead to serious
problems including coma and permanent brain damage.
What causes Isovaleric Acidaemia?
IVA occurs when a baby is born with neither copy of their gene to breakdown the amino
acid leucine functioning correctly. IVA is an autosomal recessive disorder because both
genes have an alteration (also known as a gene mutation).
Usually people eat more amino acids (building blocks of protein) than they need and the
extra amino acids are broken down. People with IVA have a problem breaking down an
amino acid called Leucine. Leucine is broken down to isovaleric acid which is normally
further broken down to make energy. People with IVA are unable to break down isovaleric
acid. This acid builds up in the body and causes harmful effects.
IVA can vary in severity and in some mild forms of IVA the risk of problems is lower.
What are the clinical effects?
IVA can affect babies in different ways. Some babies start to develop symptoms of a
metabolic crisis in the first days or weeks of life. These symptoms can include poor feeding,
irritability, sleepiness, vomiting, breathing difficulties and fast breathing, and coldness. If the
baby is not treated they may deteriorate, have fits, become unconscious and are at risk of
dying.
Sometimes a baby may not develop symptoms of a metabolic crisis until later in the first year
of life or later during childhood. In these cases a metabolic crisis may be caused by having an
illness such as an infection or upset stomach. Other children with IVA may not develop a
metabolic crisis but may have learning difficulties.
How common is Isovaleric Acidaemia?
IVA is a rare disease and affects about 1 in 155,000 babies born in the UK. It is estimated
that in Wales one baby will be born every four to five years with IVA.
What are the benefits of screening for Isovaleric Acidaemia?
Newborn bloodspot screening means that babies who have IVA can be identified early and be
given treatment, and parents can be made aware of the management of their baby if they
become unwell. If babies are not screened for IVA and they have the disorder, the diagnosis
may only be made if the baby or child develops symptoms including a metabolic crisis.
What is the treatment for Isovaleric Acidaemia?
Treatment aims to reduce the build up of toxins which can cause metabolic crisis and learning
difficulties. This is dietary management and medication and needs to be undertaken with
advice from a specialist metabolic team including specialist dietitian. The patient has a low
protein diet with the aim to reduce the amount of leucine. Foods are measured to ensure
that the right amount of protein is eaten each day with sufficient for normal growth and
development.
All baby milks (including breast milk) contain more protein than can be tolerated by babies
with IVA. Breast feeding is still encouraged but the amount of milk a baby with IVA is given
needs to be measured and controlled. A special baby milk is sometimes given to meet dietary
requirement but this depends on how much protein the child is allowed.
Medications called L-carnitine and/or glycine are used to help clear some of the toxins that
develop.
Babies and children with IVA are at risk of having a metabolic crisis when they have infections
or illnesses such as diarrhoea or vomiting. The risk of a crisis can be reduced by starting a
special feed called the emergency regimen, which is a glucose polymer, and stopping proteincontaining milk and food. Medications should also continue whilst the emergency regimen is
being given. The specialist metabolic dietitian advises parents on how to give the emergency
regimen. Parents are also advised of when they need to seek urgent medical care.
How effective is the treatment?
With early diagnosis and treatment, babies with IVA can have a low protein diet and
medication to improve their long term outlook and prevent metabolic crises. Patients will
need to use their emergency regimen during illness. This will help to reduce the risk of long
term brain damage.
What are the implications for other members of the family?
If parents have a child with IVA, the risk of them having another affected child is 1 in 4 (25%).
If the affected child has older siblings, the parents will be offered testing of those children for
IVA. If parents have other children in the future, the babies should be offered screening earlier
than routine screening. This should be undertaken between one and two days after birth.
As IVA is an inherited condition, parents can be offered and referred to specialist genetic
services for further information and advice. Other family members may have concerns about
the implications for them and can also be referred to specialist genetic services for advice
and information.
Information adapted from the information resource for parents and professionals on the Expanded Newborn Screening
Programme and Rare Conditions websites.
Further information available at: www.newbornbloodspotscreening.wales.nhs.uk
Support and information from other patients, parents and carers available from CLIMB
(www.climb.org.uk) 0800 652 3181