What is Maple Syrup Urine Disease [MSUD] and what does it do? It occurs when there is an inherited disorder present where the body cannot process certain amino acids. The unusual name comes from the odor that is detected in the urine of infants who have it. Children with MSUD typically do not feed very well, vomit often, have lethargy, and will lag behind in development when compared to other children. It’s important to get this disease treated because it can lead to death if it is not.
Statistics on Maple Syrup Urine Disease
1. From a general population standpoint, MSUD affects 1 out of every 185,000 children that are born.
2. The disorder occurs much more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns.
3. If both parents carry the MSUD gene, each of their children has a 1 in 4 chance of getting the disorder, and a 1 in 2 chance of being a carrier.
4. Among the Mennonites in Pennsylvania, as many as 1 out of every 176 babies is born with the disorder.
5. Being of the Ashkenazi Jewish population increases the chance of a child being born with MSUD by 3x over the general population.
6. There are 5 clinical subtypes of MSUD. It is also more common in people of French-Canadian ancestry.
7. MSUD is inherited in an autosomal recessive manner. It affects both boys and girls equally.
8. In the classic form of MSUD, 50% or more of the keto acids are derived from leucine and the activity of the BCKD complex is less than 2% of normal
9. Classic MSUD may be missed in newborn screening because of slow rise of blood leucine levels.
10. A 1989 study found that early or prospective treatments for MSUD can greatly improve the changes of a normal intellectual outcome for affected children.
11. Drinking fenugreek tea for an infant can actually simulate the effects of this genetic disorder because of the levels of sotolone that they contain.
12. 1 in 81 in the Ashkenazi Jewish population are carriers for this disease.
13. Genetic testing for MSUD can identify 99% of Ashkenazi Jewish carriers.
14. In Sweden, approximately 10 individuals have been diagnosed with MSUD in the past 30 years.
15. Children with the intermittent form of the disease develop normally, but will suffer periodic attacks that may cause seizures and poor motor coordination.
16. Those affected will need to avoid foods such as cow’s milk, regular formula, meat, fish, cheese and eggs. Regular flour, dried beans, nuts, and peanut butter also have BCAAs and must be avoided or strictly limited.
17. Many vegetables and fruits have only small amounts of the BCAAs and can be eaten in carefully measured amounts.
Common Symptoms and Variants
There are variants of this disease that may occur later in childhood, but the classic symptoms are seen almost immediately upon birth. Later onset versions have milder symptoms, but all forms of MSUD will eventually lead to developmental delays. The cause is a mutation that occurs in one of three different genes that are responsible for amino acid processing. It does not require a mutation of all three genes for Maple Syrup Urine Disease to be present.
Screenings for this disease occur within 24 hours in some states. Blood samples are taken from the baby’s heel so that they can have the leucine levels in their blood analyzed. Infants who have the classic form of the disease may appear normal for the first few days after birth, but afterward will begin to exhibit sings and symptoms. Left untreated, the classic form of MSUD will typically caused death before a child’s first birthday.
Treatment for this disease involves dietary restriction. Infants must be placed on amino-acid free formulas to prevent brain damage from occurring almost immediately. As children grow up, they must continue avoiding foods that have high protein levels in them to avoid having attacks happen.
Global Incident Rates
The incident rates of MSUD are rather low in the general population, which means the high rates in certain other population groups are indicative of close family arrangements. With a limited gene pool, even a single mutation can cause several carriers to appear within a family in just 2-3 generations and this can quickly increase the chances of disease development in future generations. With 1 in 81 Ashkenazi Jews being carriers and up to 1 in 176 children in the Pennsylvania Old World communities being born with active versions of the disease, anyone in these population groups should be immediately tested before having children.
The good news is that the disease can be successfully treated with severe diet restrictions. Children with MSUD will need to work with their doctors and nutritionists over time to fine tune a diet that will work for them. Although attacks can happen at virtually any time, as long as low risk foods are generally eaten, a child’s life can be relatively normal. Children who attend public school may trade lunches or sneak foods that they’re not supposed to eat, so parents may choose other schooling options where food trading is less likely.
It is a disease that may be difficult for some to manage, but as long as it is caught early on in life, it doesn’t have to be a death sentence. Most states in the US and many developed countries have been testing for this genetic disease at birth since 2010. Successfully living with MSUD usually requires ongoing support because of the difficulties of living with an inherited metabolic disorder and the consistent blood testing to check amino acid levels, but it does not affect intellectual levels when caught quickly enough.
For the average parent, Maple Syrup Urine Disease is not a disorder that needs to be worried about. The chances of a mutation in the general population is extremely slight. By being aware of the statistics of MSUD, however, parents will know what to do if one of the versions of this disease makes itself known.