Maple syrup urine disease (MSUD): symptoms, newborn screening, diet and treatment

When we eat protein the body breaks it down 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 related substances build up to high and harmful levels in the blood and the brain.

The name is a reference to a characteristic sweet smell associated with the condition, but in England it is the newborn blood spot screening test, not the smell, that normally leads to diagnosis.

Because a baby needs a faulty copy of the gene from each parent, the condition can come as a complete surprise to a family with no history of it.

NHS England says babies with MSUD may present with feeding problems, sleepiness and abnormal movements even before the newborn screening result is reported, and can progress to have fits and slip into a coma, which can lead to severe brain damage and can be life-threatening.

During later illness, the symptoms of a metabolic crisis (also called metabolic decompensation) are listed in the detailed information leaflet.

• Irritability.

• Sleepiness and non-responsiveness.

• Floppiness and falling over.

• Poor feeding.

• Breathing difficulties.

• Seizures and coma.

In England the newborn blood spot screening test, the heel prick test, is offered when a baby is about 5 days old. NHS England says it measures the amount of some amino acids in the blood and that a high level of leucine suggests the baby may have MSUD.

If the result is screen positive, the metabolic team contacts the family and tells them to take the baby immediately to the local hospital for admission, even if the baby seems well. Treatment starts on the basis of the screening result, because the condition can be life-threatening, while blood tests confirm the diagnosis. The local hospital then arranges transfer to a metabolic specialist centre.

Many babies with MSUD are already unwell and in hospital before the screening result is reported, which is why any newborn with poor feeding, unusual sleepiness or movements needs urgent medical assessment whatever the screening result says.

NHS England says that if a baby is very sick they are likely to need intensive care, and it is very important to bring down high leucine levels as quickly as possible. Breast feeds and normal infant formula are temporarily stopped and the baby is started on a specialised MSUD infant formula without leucine, isoleucine or valine. Some babies need haemodialysis to filter harmful substances from the blood. Mothers who want to breastfeed are encouraged to express milk so that it can be restarted when leucine levels are lower.

The long-term plan, set by the metabolic team and dietitians, is built on a restricted protein diet. The detailed leaflet describes limited daily breastmilk or infant formula, a leucine, isoleucine and valine free formula, and sometimes isoleucine and valine supplements, with weekly blood tests in the first year and home blood tests posted to the metabolic laboratory. GPs are asked to prescribe the specialist formula and supplements.

Ordinary illnesses can push levels up because the body breaks down its own protein under stress. NHS England says signs of illness may include fever, vomiting, cough or cold, sore throat, chest infection, diarrhoea or the baby not being their usual self. You should start the emergency regimen if your baby becomes unwell or is not tolerating usual feeds and contact the metabolic team at the start of any illness.

You should take your baby to hospital immediately if they do not tolerate the emergency regimen or their symptoms are getting worse, taking with you the emergency regimen instructions, the specialist formulas and supplements and the glucose polymer. The emergency regimen guidelines are published by the British Inherited Metabolic Diseases Group.

This is a condition where a calm, rehearsed plan makes a real difference, and families are taught how to look after their child during illness.

NHS England says that other children from the same parents have a 1 in 4 chance of having MSUD, and that the metabolic team will discuss whether testing is necessary for brothers and sisters. A new baby from the same parents also has a 1 in 4 chance. Parents are advised to tell their midwife and GP about the family history of MSUD when they find out they are pregnant, and to inform their metabolic team early.

NHS England points families to their metabolic team and to Metabolic Support UK for further information and support.

NHS England says newborn screening allows the diagnosis to be made early, which can improve the long-term outcome. Without prompt treatment it can lead to long-term health problems including brain damage, severe learning and physical difficulties and behavioural problems.

The condition needs lifelong management and the detailed leaflet stresses that following dietetic instructions is very important for your baby's health. The metabolic team sees families regularly throughout the child's life and the child remains under their care.

In the UK, MSUD care is delivered by NHS specialist metabolic centres following a positive screening result, with local hospitals and GPs supporting day-to-day prescribing and emergency treatment. There is no routine role for private care in diagnosis because screening is part of the NHS programme, and the specialised formulas are provided through NHS prescribing.

Families sometimes seek a second opinion or genetic counselling privately. Whichever route is used, the emergency plan from the specialist metabolic team should stay the reference for illness.