The Biochemistry :
Maple Syrup Urine Disease is caused by a gene defect that is passed down from the family. This metabolic deficiency causes three amino acids ; Valine, Leucine and Isoleucine from being decarboxylated.
The three amino acids will first be transaminated to form their alpha-ketoacid and alpha-hydroxy acids, before undergoing oxidative decarboxylation.
The lack of branched chain alpha-ketoacid dehydrogenase (BCKDH) causes the failure of oxidative decarboxylation.
Therefore, high amounts of branched chain amino acids, their alpha-ketoacids and alpha-hydroxy acids are accumulated in the blood,urine as well as cerebral fluid.
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What it causes :
The accumulation of such chemicals would cause many problems such as neurological disorders, mental retardation or even death.
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Variants of MSUD :
There are many types of Maple Syrup Urine Disease, and some of them are mentioned below :
1) Complete lack of Branched Chain Alpha-Ketoacid Dehydrogenase(BCKDH).
This is the classic MSUD, which happens in 1 in 200,000 neonates.
The complete lack of the enzyme in the mitochondria means that NONE of the chemicals are being decarboxylated. It is highly life threatening.
2) Mild to Intermediate activity
Activity of of Dehydrogenase enzyme is present, however it is only approximately 5 to 25 percent of normal activity. Excessive vomiting is one of the more problematic symptoms for people suffering from Mild - Intermediate MSUD.
3) Intermittent and random
Children who possess the defect may suddenly have MSUD in later parts of their childhood due to some kind of physical stress such as fever or infections. It can be as severe as the complete lack of activity, and can be extremely fatal. If fortunate, it would only resemble Intermediate MSUD.
4) Thiamine-responsive
Has about 20% of decarboxylase activity, but has 3 times as many chemicals as normal.
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