MSUD is inherited and shows symptoms soon after birth. Although Classic MSUD is the most common form, there are several variations.
Inherited Disorder
MSUD is an autosomal recessive disorder in which the enzyme needed to metabolize several essential amino acids is defective. The enzymes affected are the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine which build up to toxic levels without treatment.
Each parent of a child with MSUD carries one abnormal gene for MSUD and one normal gene. Parents are called “carriers” and are not affected by the disorder as the normal gene is dominant (expressed). A child with MSUD has received an abnormal gene from each parent.
When both parents are carriers, there is a 1 in 4 chance with each pregnancy that the baby will receive an abnormal gene from each parent and develop MSUD; a 2 in 4 chance the baby will receive one abnormal and one normal gene, thus becoming a carrier of MSUD; and a 1 in 4 chance the baby will receive two normal genes. Persons with two normal genes cannot pass MSUD to their offspring.
Because a person with MSUD has two abnormal genes, a child born to that person will automatically be a carrier. However, the child will not have MSUD unless the other parent also has MSUD or is a carrier.
Symptoms of MSUD
Maple Syrup Urine Disease includes both classic and variant types. The symptoms of classic MSUD are usually evident within the first week of life and include poor feeding, irritability, and the characteristic odor of maple syrup in the urine and earwax. Within days, infants may lose their sucking reflex and grow listless, develop a high-pitched cry, and become limp with episodes of rigidity. Illness and infection can cause a life-threatening metabolic crisis at any age. Without diagnosis and treatment, symptoms progress rapidly to seizures, coma, and death.
Types Of MSUD
Variant forms of MSUD are milder and often not diagnosed until illness and infection cause symptoms to emerge. In variant types, failure to thrive may be the first symptom noticed.
Four general classifications are used to identify the types of MSUD: classic, intermediate, intermittent and thiamine-responsive. These terms refer to the amount and type of enzyme activity present in the affected child, which can vary considerably within each classification.
Classic MSUD
Classic is the most common type of MSUD. In classic MSUD, little or no enzyme activity (usually less than 2% of normal) is present. Infants with classic MSUD will show symptoms within the first several days of life. They generally have poor tolerance for the BCAAs, so protein must be severely restricted in their diet.
Intermediate MSUD
Intermediate MSUD is a variant of the classic type of the disease. Those with intermediate MSUD have a higher level of enzyme activity (approximately 3-8% of normal). They can usually tolerate a greater amount of leucine. However, when ill or fasting, the child with intermediate MSUD reacts just like a child with classic MSUD. Management is similar for the intermediate and classic types of MSUD.
Intermittent MSUD
Intermittent MSUD is a milder form of the disease because of the greater enzyme activity present (approximately 8-15% of normal). Often the child does not have symptoms until 12 to 24 months of age, usually in response to an illness or surge in protein intake. During episodes of illness or fasting, the BCAA levels elevate, the characteristic maple syrup (or burnt sugar) odor becomes evident, and the child can go into a metabolic crisis.
Thiamine-responsive MSUD
Thiamine-responsive MSUD is basically just what the name implies. Giving large doses of thiamine to the thiamine-responsive child will increase the enzyme activity which breaks down leucine, isoleucine and valine. In most cases only moderate protein restriction is needed for this more rare type of MSUD.