Propionic acidaemia: an inherited metabolic condition explained

Propionic acidaemia, usually shortened to PA, is a rare inherited metabolic condition. The UK National Screening Committee places it with a group called organic acid disorders, which it describes as rare inherited disorders in which the body is not able to break down certain types of amino acids and fats, leading to a build-up of harmful compounds that can damage vital organs such as the brain, heart and liver.

The teaching booklet produced by metabolic dietitians of the British Inherited Metabolic Disease Group (BIMDG) explains the mechanism in simple terms. Protein in food is broken down into amino acids by enzymes. In PA the body lacks an enzyme called propionyl-CoA carboxylase, so it cannot break down four amino acids, and propionic acid and other chemicals accumulate in the blood and urine. Propionic acid also comes from the breakdown of fatty acids used for energy when the body has gone a long time without food, and from gut bacteria.

The same booklet explains that a build-up of harmful chemicals can damage the brain and kidneys and cause problems in other organs, and may delay development such as walking and talking. The severity and age of onset vary, which the National Screening Committee also notes.

The BIMDG booklet says symptoms commonly begin in the first few days of life. It lists poor feeding, vomiting, dehydration, a floppy baby, excessive sleepiness, rapid breathing and seizures, and states that the effects of PA quickly become life-threatening if unmanaged.

A baby who is very sleepy, not feeding, vomiting or breathing fast needs urgent medical assessment, whatever the cause. In the UK that means calling 999 or going to A&E for a baby who is seriously unwell, or contacting NHS 111 for advice if you are unsure. For children already diagnosed with PA, the family will have a written emergency plan from their metabolic team and should follow it.

Later in life, illness or going too long without food can cause a metabolic crisis. The booklet describes this as a build-up of propionic acid and other toxic chemicals such as ammonia, usually triggered by childhood illnesses such as vomiting and diarrhoea or by fasting for too long.

The BIMDG booklet says PA is diagnosed by measuring chemicals containing propionic acid in the blood and urine, and can also be diagnosed by looking at enzyme levels and at the body's genes.

The UK National Screening Committee reviewed organic acid disorders, including PA, in 2016 and does not currently recommend newborn screening for them. It gave the reasons that the quality of evidence is not high enough to show whether screening is of long-term benefit, that not enough is known to identify who will be severely affected and who will not, and that it is unclear how to treat babies detected at screening who show no signs of illness. The NHS blood spot test for newborn babies checks for a defined list of inherited metabolic diseases, and PA is not among those listed on the NHS page.

The booklet explains that the aim is a balance: enough protein for growth and repair, but not so much that toxic chemicals are made. Management therefore combines a protein-restricted diet with a sufficient energy supply, regular feeding, carnitine medication and antibiotics to control gut bacteria, with other medications where necessary. Tube feeding may be necessary to give regular feeds and ensure energy, nutrient and fluid needs are met.

Monitoring includes frequent blood tests to check amino acids, nutrients and other chemicals, height and weight measurements and developmental checks, and diet and medicines are adjusted according to age, weight and blood chemical levels.

The booklet also gives practical hints: keep a good supply of dietary products and medicines and check they are in date, keep emergency feed products and a written emergency plan, and keep supplies of medicines to control fever, which should be given as normally recommended.

During any childhood illness, the booklet says an emergency regimen is given to avoid a lack of energy supply and the build-up of harmful chemicals that cause a metabolic crisis. Protein in food and drink is stopped, an emergency feed made up of glucose polymer is started, and medication continues as prescribed.

The checklist for illness says to take the full amounts of emergency feeds as prescribed, to go immediately to hospital if symptoms continue or you are worried, and to keep the metabolic team updated. Its key message is that it is imperative that emergency feeds are started promptly and there are no delays in management.

• Stop protein in food and drink during illness, as directed by your metabolic team.

• Start the emergency regimen promptly and take the full amounts prescribed.

• Continue medicines as prescribed.

• Go to hospital immediately if symptoms continue or you are worried.

• Keep your metabolic team informed.

PA is inherited in an autosomal recessive way. The booklet explains that everyone has a pair of genes that make the enzyme; in a child with PA neither works correctly, and the child inherits one non-working gene from each parent. The parents are carriers and do not have PA, because their other gene works correctly. It stresses that there is nothing that could have been done to prevent the baby having PA.

When both parents are carriers, in each pregnancy there is a 25% chance (1 in 4) that the baby has PA, a 50% chance (1 in 2) that the baby is a carrier, and a 25% chance (1 in 4) that the baby has two working genes and is neither affected nor a carrier. Families can ask their metabolic or genetics team about testing and options.

The booklet calls PA a serious inherited metabolic disorder that can lead to severe problems, managed with a protein-restricted diet, regular feeding and medications. Outcomes vary widely between individuals, and the sources read for this page do not give survival or long-term outcome figures, so these are best discussed with a specialist metabolic team.

Care is delivered by specialist metabolic dietitians, nurses and doctors, and the booklet suggests families keep a list of who is who in the team with contact details. Organisations such as Metabolic Support UK, named in the booklet, offer wider support, and the booklet points to a low-protein cooking and lifestyle website for practical advice.