Maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited genetic disorder in which the body is unable to process certain amino acids properly, unmetabolised amino acids are passed in the urine giving it a distinctive maple syrup odour.

Symptoms

From early infancy, the condition is characterized by poor feeding, vomiting, lack of energy (lethargy), seizures, and mental retardation. The urine of affected infants has a distinctive sweet odor, much like burned caramel, that gives the condition its name. Maple syrup urine disease can be life-threatening if left untreated.

Maple syrup urine disease can be classified by its pattern of signs and symptoms or by its genetic cause. The most common and most severe form of the disease is the classic type, which appears soon after birth. Variant forms of the disorder appear later in infancy or childhood and are typically less severe, but still involve mental and physical retardation if not treated.

There are several variations of the disease:

• Classic Severe MSUD
• Intermediate MSUD
• Intermittent MSUD
• Thiamine-responsive MSUD
• E3-Deficient MSUD with Lactic Acidosis
• Fenugreek Tea

Genetics

Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide.

Mutations in the BCKDHA, BCKDHB, DBT, and DLD genes cause maple syrup urine disease. These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (particularly protein-rich foods such as milk, meat, and eggs). Mutations in any of these genes reduce or eliminate the function of the enzyme complex, preventing the normal breakdown of leucine, isoleucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.

Reference

• National Library of Medicine. Genetics Home Reference, Maple syrup urine disease