Maple Syrup Urine Disease, Metabolic Disorder, Amino acid disorder Screening -Infant

Maple Syrup Urine Disease, Metabolic Disorder, Amino acid disorder Screening -Infant

Maple Syrup Urine Disease, Metabolic Disorder, Amino acid disorder Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both genders

The genetic screening for Maple Syrup Urine Disease is recommended.

B

Maple syrup urine disease (MSUD) is a rare genetic disorder characterized by deficiency of certain enzymes (branched-chain alpha-keto acid dehydrogenase complex) required to break down (metabolize) the three branched-chain amino acids (BCAAs) [Leucine, Isoleucine and Valine] in the body. The result of this metabolic failure is that all three BCAAs, along with their various byproducts, accumulate abnormally throughout the body.

OVERVIEW

Maple syrup urine disease (MSUD) is caused by a defect in branched-chain ketoacid dehydrogenase (BCKD), which is a multi-enzyme complex with 4 components found in mitochondria in liver, kidney, muscle, and fibroblasts. The enzyme is responsible for the degradation of oxoacids. Accumulation of leucine and its corresponding branched-chain keto acid (BCKA), alpha-ketoisocaproic acid (alpha KIC), disturbs brain cell volume regulation with consequent brain edema and secondary impairment of neuron growth, myelin synthesis, and cerebral neurotransmitter production. These can cause death, intellectual and other disability.

SCREENING

Finding

Elevated leucine and leucine/alanine ratio

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.99%; milder forms of the disease can be missed by newborn screening.

PREVALENCE

The incidence of MSUD in the USA is approximately 1:198,000. 

INHERITANCE

MSUD is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing or enzyme analysis by amniocentesis or CVS

CLINICAL CHARACTERISTICS

With treatment before crises, normal IQ and development can be expected. Without treatment, profound mental retardation and neurologic disturbances can be expected. Brain edema can lead to cerebellar herniation, compression of the brain stem, and death, especially in older individuals.

Initial symptoms, beginning with protein ingestion, may include:

  • A maple syrup odor of cerumen, which can be present by 3 days of age
  • Elevated branched-chain amino acids, leucine, isoleucine, and valine; presence of allo-isoleucine detectable shortly after birth, but can be missed by the newborn screening in milder forms of the disease or if the sample is obtained too early (<12h after birth)
  • Ketonuria becomes evident after branched-chain amino acids become elevated

 

Because of the rapidity of onset, severe symptoms may be present before screening results are reported or treatment begins.

EARLY SIGNS

Forms of maple syrup urine disease (MSUD) vary widely in the severity of their signs. “Classic MSUD” is the most common form and is seen in babies.

Babies with classic MSUD usually begin showing signs shortly after birth. These signs include:

  • Poor appetite
  • Trouble sucking during feeding
  • Weight loss
  • High pitched cry
  • Urine that smells sweet like maple syrup or burnt sugar
  • Sleeping longer or more often
  • Tiredness
  • Irritability
  • Vomiting
  • Developmental delays

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

CAUSES

When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, called amino acids. Other enzymes break down the amino acids. In maple syrup urine disease (MSUD), the group of enzymes called branched-chain ketoacid dehydrogenase (BCKAD) complex is not working correctly.

BCKAD is a group of four enzymes that work together to break down the amino acids leucine, isoleucine, and valine for energy. You may hear these called the branched-chain amino acids. These three amino acids all share a similar branched shape.

If your baby has MSUD, then his or her body is lacking one or more of the enzymes in the BCKAD complex. This causes the BCKAD group not to work correctly. When BCKAD is not working, your baby’s body cannot break down the branched chain amino acids. The amino acids then build up in the blood. High levels of these amino acids in the blood can be toxic.

MSUD is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for MSUD, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with MSUD is rare, when both parents are carriers, they can have more than one child with the condition. 

TREATMENT

Dietary Treatment

Your baby may need to be on a protein-restricted diet to avoid foods containing proteins that your baby’s body cannot break down. A dietician can help you plan the best diet for your child. Special formulas and foods for children with maple syrup urine disease (MSUD) are also available. These formulas will likely need to continue through adulthood.

Supplements and Medications
Thiamine supplements are helpful for some children with MSUD. Your baby’s doctor will be able to determine if your baby has a type of MSUD that is considered “thiamine-responsive” and write an appropriate prescription.

EXPECTED OUTCOMES

If maple syrup urine disease (MSUD) is treated early, children can have healthy growth and development.

Some children may still experience signs of MSUD even with treatment.

It is important to treat MSUD because babies who do not receive treatment are at risk for brain damage, coma, or death.