Maple syrup urine disease: genes, newborn screening and treatment in the UK

When we eat, the body breaks protein in food into smaller parts called amino acids, and enzymes then break these down further so they can be used. NHS England explains that in MSUD an enzyme called branched-chain keto-acid dehydrogenase is missing, which leads to problems breaking down three amino acids: leucine, isoleucine and valine. Leucine and other related substances then build up to high and harmful levels in blood and the brain.

Babies with MSUD may show feeding problems, sleepiness and abnormal movements, even before the newborn screening result is reported, and they can go on to have seizures and slip into a coma, which can be life-threatening.

If MSUD is not treated promptly, NHS England says it can lead to long-term health problems including brain damage, severe learning and physical difficulties, and behavioural problems. Newborn screening allows the diagnosis to be made early, which can improve the long-term outcome.

MSUD is inherited in an autosomal recessive way. A baby inherits two faulty copies of the gene, one from each parent. The parents each carry one faulty copy and are usually well, so there is often no family history before the first affected baby.

NHS England says children from the same parents have a 1 in 4 chance of having MSUD, and that a new baby from the same parents also has a 1 in 4 chance. The metabolic team discusses whether testing is needed for other children.

When a family knows there is MSUD in the family and a new pregnancy begins, the parents should tell their midwife and GP about the family history and inform the metabolic team early in the pregnancy. The metabolic team writes a birth plan, which includes an early screening test for the new baby between 12 and 24 hours after birth, in addition to the routine blood spot test.

The NHS says the newborn blood spot test is recommended for all babies and is normally done when a baby is 5 days old, usually by a midwife, with results by the time the baby is 6 weeks old or sooner depending on the result. MSUD is one of the inherited metabolic diseases the test checks for.

NHS England explains that the test measures the amount of some amino acids in the blood and that a high level of leucine suggests MSUD, which is called a screen positive result. If a baby has a screen positive result, the metabolic team contacts the parents and instructs them to take the baby immediately to the local hospital for admission, even if the baby is well.

Blood tests confirm the diagnosis, but treatment starts based on the screening result because the condition can be life-threatening. Many babies with MSUD will already be unwell and may be in hospital before the result is reported.

NHS England says the priority at first is to bring down the leucine level as quickly as possible. Breast feeds and normal infant formula are stopped temporarily and the baby starts a specialised MSUD formula that contains no leucine, isoleucine or valine. Some babies need haemodialysis to filter the blood, and very sick babies are likely to need intensive care. Mothers who wish to breastfeed are encouraged to express milk, which can be restarted once leucine is much lower.

Long-term treatment is a restricted protein feeding plan. This combines a limited daily volume of breast milk or ordinary infant formula with the leucine, isoleucine and valine free formula and supplements of isoleucine and valine where needed. There are weekly blood tests during the first year, and families learn to take home blood tests which are posted to the metabolic laboratory. GPs are asked to prescribe the special formula and supplements, and a metabolic dietitian adjusts feeds to the blood results and weight.

The metabolic team sees the child regularly throughout life, and following the dietary instructions is described as very important for the child's health.

NHS England describes a metabolic crisis, also called metabolic decompensation, as a rapid build-up of leucine that can make a child severely unwell. Symptoms include irritability, sleepiness and non-responsiveness, floppiness and falling over, poor feeding, breathing difficulties, seizures and coma.

To prevent this, parents are taught the emergency regimen, which consists of MSUD specialist formula, isoleucine and valine supplements and glucose polymer powder given regularly day and night. It is started if the child becomes unwell or is not tolerating usual feeds, and the metabolic team should be told at the start of any illness. Signs of illness include fever, vomiting, cough or cold, sore throat, chest infection, diarrhoea or not being their usual self.

A child should be taken to hospital immediately if they do not tolerate the emergency regimen or are getting worse, taking along the regimen instructions, the British Inherited Metabolic Diseases Group guidelines and the formula and supplements.

NHS England signposts families to Metabolic Support UK, and to the British Inherited Metabolic Diseases Group website, which holds the emergency regimen guidelines and a booklet about MSUD. The metabolic team is the first contact for questions about feeding, illness and school.