6th February 2024

Maple Syrup Urine Disease

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder affecting the body’s ability to break down certain amino acids. It is named after the characteristic sweet smell of the affected individual’s urine, which resembles maple syrup.

This condition is caused by mutations in one of several genes for enzymes involved in the metabolism of branched-chain amino acids (BCAAs), including leucine, isoleucine and valine. Usually, these amino acids are broken down by specific enzymes and converted into other molecules that the body can use for energy. However, these enzymes are deficient or defective in individuals with this condition, accumulating branched-chain amino acids and their by-products in the blood and tissues.

Clinical features

Clinical features of maple syrup urine disease depend on the location of BCAA accumulation. The severity and age of onset can also vary depending on the specific gene mutations and enzyme activity levels.

• Brain
  • Accumulation of BCAAS and their by-products in the brain is toxic and can cause brain damage and multiple other neurological sequelae, including seizures, coma and even death.
• Urine
  • The characteristic sweet smell of urine gives this condition its name.
• Other
  • Many symptoms are non-specific. Newborns with the condition may initially appear normal but develop symptoms within a few days, including irritability, vomiting, poor feeding, failure to thrive and an unusual body odour.

Some less severe forms of MSUD show late expression of symptoms – in late infancy, childhood or even adulthood. These intermittent forms tend to be characterised by episodes of metabolic decompensation triggered by stressors like illness or fasting.

Diagnosis

Diagnosis of MSUD tends to be made through a newborn screening programme – the heel prick test. The blood sample is tested for BCAAs and their by-products, with elevated levels indicating the presence of the disorder. Confirmatory tests are then performed to confirm the diagnosis and identify specific gene mutations responsible.

Management

Lifelong management of MSUD involves a low-protein diet, often tailored explicitly by a specialist metabolic dietitian. The role of this is to limit the intake of BCAAs, and it involves limiting high-protein foods such as meat, fish, cheese, eggs, pulses and nuts. Breast milk and baby formula need to be monitored before feeding affected babies. Regular baby formula is high in amino acid content, so it often needs to be switched to a particular formulation.

Although BCAAs are limited in the diet, some children must take isoleucine and valine supplements to maintain healthy levels within a prescribed range. Regular blood tests are required to monitor these levels.

Sometimes, liver transplantation can be used to treat MSUD, allowing patients to have a regular diet without the risk of metabolic crisis. However, liver transplantation is a significant procedure with its risks; patients have to take immunosuppressant medications for the rest of their lives, and therefore, it is not an option for all patients.