MSUD is inherited disorder that ends up in progressive nervous system degeneration and for some, brain damage. The hereditary defect that produces MSUD comes from a defect within the enzyme called branched-chain alpha-keto acid dehydrogenase (BCKD), an important ingredient for the breakdown of certain amino acids (leucine, isoleucine, valine). In the absence of the BCKD enzyme, these amino acids build up to toxic levels within the body.

The name MSUD comes from the fact that when the blood amino acid levels are high, urine takes on the syrup’s distinctive odor. 1 out of every 185,000 babies born in the world are detected with MSUD.

The four types of maple syrup urine disorders are:

  1. Classic
  2. Intermediate
  3. Intermittent
  4. Thiamine-response

Other names for this condition

  • BCKD deficiency
  • Branched-chain alpha-keto acid dehydrogenase deficiency
  • Branched chain ketoaciduria
  • Ketoacidemia
  • MSUD

Causes

MSUD is generated by the modification in the genes DBT, BCKDHB and BCKDHA. These genes provide instructions for making proteins that work together as part of a complex.

Mutations in any of these 3 genes prevent normal breakdown of leucine, isoleucine, and valine, reducing functions of the protein complex. As a result, these amino acids and their byproducts build up in the body leading to complications.

Symptoms

  • Poor appetite
  • Sleepiness or lack of energy
  • Vomiting
  • Poor weight gain
  • Fast and shallow breathing
  • Maple sugar smell in the earwax, sweat, or urine
  • Changes in muscle tone, muscle spasms, and seizures
  • Delayed development

Diagnosis

Screening for Maple Syrup Urine Disorder

Newborn screening for MSUD is done using a small amount of blood collected from your baby’s heel. It involves analyzing the blood of 1–2-day-old newborns through tandem mass spectrometry. The blood concentration of leucine, isoleucine and valine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids.

Treatment and management

Diet low in protein:

Most natural foods contain some protein. Thus, any food intake must be closely monitored, and day-to-day protein intake calculated on a cumulative basis to ensure individual tolerance levels are not exceeded at any time.

Special formulae:

As the MSUD diet is protein-restricted, and adequate protein is a requirement for all humans, tailored metabolic formula containing all the other essential amino acids, as well as any vitamins, minerals, omega-3 fatty acids and trace elements are an essential aspect of MSUD management.

Monitoring:

Careful monitoring of the isoleucine, leucine and valine levels in the blood helps in maintaining MSUD under control. Nutritional analysis of the blood draws and regular metabolic consultations are recommended.

Prevention:

With two defective copies of the BCKD gene there are no methods for preventing the manifestation of the pathology of MSUD in infants. However, DNA testing can be done for screening of the disease with the consultation of genetic counselors. DNA testing also helps identify the disease in an unborn child.