The disease is estimated to affect 1 out of 185,000 infants worldwide and its frequency increases with certain heritages.Newborn screening for maple syrup urine disease involves analyzing the blood of 1–2 day-old newborns through tandem mass spectrometry. The blood concentration of leucine and isoleucine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids. Once the newborn is 2–3 days old the blood concentration of branched-chain amino acids like leucine is greater than 1000 μmol/L and alternative screening methods are used. Instead, the newborns urine is analyzed for levels of branched-chain alpha-hydroxyacids and alpha-ketoacids.The amount and type of enzyme activity in an affected individual with MSUD will determine which classification the affected individual will identify with:
Classic MSUD: Less than 2% of normal enzyme activity
Intermediate MSUD: 3-8% normal enzyme activity
Intermittent MSUD: 8-15% of normal enzyme activity
Thiamine-Responsive MSUD: Large doses of thiamine will increase enzyme activity. Classification
Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of this disease is the classic type, which appears soon after birth, and as long as it remains untreated, gives rise to progressive and unremitting symptoms.
Variant forms of the disorder may become apparent only later in infancy or childhood, with typically less severe symptoms that may only appear during times of fasting, stress or illness, but still involve mental and physical problems if left untreated.Sub-divisions of MSUD:
Classic MSUD
Intermediate MSUD
Intermittent MSUD
Thiamine-responsive MSUDGenerally, majority of patients will be classified into one of these four categories but some patients affected by MSUD do not fit the criteria for the listed sub-divisions and will be deemed unclassified MSUD. Prevention
There are no methods for preventing the manifestation of the pathology of MSUD in infants with two defective copies of the BCKD gene. However, genetic counselors may consult with couples to screen for the disease via DNA testing. DNA testing is also available to identify the disease in an unborn child in the womb. Treatment
Monitoring
Keeping MSUD under control requires careful monitoring of blood chemistry, both at home and in a hospital setting. DNPH or specialised dipsticks may be used to test the patients urine for ketones (a sign of metabolic decompensation), when metabolic stress is likely or suspected. Fingerstick tests are performed regularly and sent to a laboratory to determine blood levels of leucine, isoleucine, and valine. Regular metabolic consultations, including blood-draws for full nutritional analysis, are recommended; especially during puberty and periods of rapid growth. MSUD management also involves a specially tailored metabolic formula, a modified diet, and lifestyle precautions such as avoiding fatigue and infections, as well as consuming regular, sufficient calories in proportion to physical stress and exertion.