Pedigree

Harrison is the affected individual and has Maple Syrup Urine Disease. He has three siblings. His brother Jack and 2 sisters Abby, and Katie. Their parents are Allison and Mark. Mark has 2 sisters, Miranda and Chelsey. His parents are Ms. Shapiro and Mr. Shapiro. Allison has a sister Rachel and their parents are Mr. and Ms. O’Donald.

Harrison inherited this disease through the inheritance of 2 homozygous recessive genes that code for the disease. The only possible way for this to happen is if Harrison’s parents are carriers or affected. Neither parent is affected and therefore they both have to be carriers for Harrison to be born with the disease. If one was a carrier and the other was homozygous dominant then all children would have 50% chance of being carriers and 50% chance of being healthy. Therefore, the only combination in which parents can have a child with MSUD, but not have the disease is if they are both carriers.

If you have MSUD and follow the prescribed diet you can have children. However, it would be wise to have children with an individual who is homozygous dominant so none of your children will inherit the disease and they will just be carriers. There is a 100% chance that your children will not have the disease and just be carriers in that instance. However, if you have children with an individual who is a carrier, Rr, and you are RR then there is a 50% chance of the child being affected and a 50% chance of the child being a carrier. You should seek the help from a genetic counselor in that case.

In Allison and Mark’s case, based on their genotypes, 50% of their children would be carriers, 25% affected, and 25% nothing. Since they had four kids, and Harrison was affected, 2 of the children, based on probability, should be carriers, and 1 should be nothing. The parents also know that none of their other children were affected because they took a test as soon as they were born. The sibling who is neither a carrier nor affected cannot have an affected child, regardless of whom they mate with. The two carriers can have an affected child if they mate with an affected individual or carrier. To prove this you must use a punnett square to determine the outcome.

PUNNET SQUARES

	R	r
R	RR	Rr
r	Rr	rr

Children of Allison and Mark

	R	R
r	Rr	Rr
r	Rr	Rr

If Harrison mates with a Homozygous Dominant individual all children are carriers but not affected

	R	r
r	Rr	rr
r	Rr	rr

50% of children will be affected if he mates with heterozygous individual

	R	r
R	RR	Rr
R	RR	Rr

The healthy child, who is not a carrier, has no chance of their children being affected

	R	R
R	RR	RR
r	Rr	Rr

Carriers can have children who are 50% carriers and 50% healthy

BIBLIOGRAPHY

"Maple syrup urine disease - Genetics Home Reference." Genetics Home Reference - Your guide to understanding genetic conditions. N.p., n.d. Web. 16 May 2011. <http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease>.

"Maple Syrup Urine Disease (MSUD)." Learn.Genetics™. N.p., n.d. Web. 16 May 2011. <http://learn.genetics.utah.edu/content/disorders/whataregd/msud/>.

"Maple syrup urine disease - PubMed Health." National Center for Biotechnology Information. N.p., n.d. Web. 16 May 2011. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001411/>.

A Glance into the Future

Blog 6:
20 years into the future

I haven’t kept up with the journal I wrote about Harrison’s severe condition, but I figured it is better late than never. I am sure you are all curious about the health of Harrison, but you will have to hold your horses. I am now 33 years old and I graduated from Yale University and Harvard Medical School. Surprisingly, Harrison was the reason I did so well in school. I always had him in mind and a goal  in mind that I would find the cure for MSUD. I can’t say that I have done that, but every time I see Harrison it makes me work that much harder at it. I did become a scientist, but it is extremely difficult to raise enough money about a very unknown disease. Harrison tells me not to worry or stress myself out about it. He says he lives a perfectly comfortable life and he is just appreciative that he is still alive. I know he is lying. I can see it in his eyes. He wants to do what every other 21 year old can do. He cannot eat what everyone else can. He also knows that if he even tries to sway from the diet, he will have another episode like he did when Abby fed him the wrong food. Although MSUD has greatly affected his life, he imagines how it would affect his daily routine if he didn’t abide by the diet. He couldn’t participate in sports, learning, or anything of that matter because he would become a “vegetable”. He would go into a coma and die. He is thankful for that and he takes each day by day. He enjoys being with his family and MSUD has made him look at life in a more positive way. Life is precious and we shouldn’t take it for granted.

Happy Birthday!

Blog 5:
Almost a year later

The other day Harrison turned one. He looked so happy, if only he knew how hard it is going to be in the future. He will always have to think about what he puts in his mouth. I feel badly and I don’t understand why bad things happen to good people. I went online wondering if any research was being done to permanently prevent MSUD. I soon realized that was not possible. There are many diets one can go on and there are the tests to diagnose a child. The best one could do is make a prediction using a pedigree and decide whether or not they should have children. Sadly, there is no permanent solution. I also looked up which gene causes the child to have MSUD. The gene that is responsible
for the disease occurs when there are mutations on chromosome 19 in the BCKHDA, BCKDHB, DBT, and DLD gene. These four genes offer instructions for making proteins that work together as a team. This protein is essential for breaking down BCAA’s. Mutations in any of these four genes reduce or eliminate the function of the protein complex, preventing the normal breakdown of BCAA’s. As a result, these amino acids and their byproducts build up in the body. High levels of these substances are toxic to the brain and other organs and their buildup leads to the serious medical problems associated with maple syrup urine disease. This whole experience has made me realize what I want to be in the future. A scientist. I want to study this disease and I am determined to find a permanent solution. Maybe I can create a way in which the gene can work without the six proteins working together. Who knows? You just have to think positively

Diet gone terribly wrong

Blog 4:

We were driving home from the Hospital because they finally discharged my mother. However, they told my family to be careful with what we feed Harrison. As soon as we got back Harrison started to cry and we knew he was hungry. We were given a huge list of foods that Harrison could not eat. This includes cow’s milk, regular formula, meat, fish, cheese, eggs, regular flour, dried beans, nuts, peanut butter and so much more. However, Abby thought it would be funny to secretly feed Harrison the foods she knew he could not eat. Eventually, our family new something was wrong. Within three or four days of Abby doing so, Harrison lost his appetite completely and refused to eat anything we put in front of him. He would also sleep for hours on end, he was vomiting, but worst of all his pee was sweet-smelling. Then we knew something was wrong. We just couldn’t figure it out and if we didn’t figure it out soon the symptoms would start to worsen. Eventually, Harrison would have seizures, go into a coma and then die. Also, MSUD attacks the brain cells because the amino acids that Harrison can’t break down are toxic to the brain. Thankfully, Abby confessed and Harrison’s diet returned back to normal. He started his special medical formula as a substitute for milk. This formula gives him the nutrients and protein he needs while helping keep his BCAA (leucine, isoleucine, and valine) levels low. As soon as we knew it, Harrison was like every other baby.

Need to do some Research

Blog 3:
I did some research and found out about the disease.  As I said before it is a potentially deadly disease and it occurs when the body is not able to break down three amino acids: leucine, isoleucine and valine. These amino acids should be used for energy or just recycled. Six proteins act as a team to break them down, but people who have a deficiency for one of the six proteins have MSUD. Since these proteins don’t function as a team, these three amino acids cannot be broken down and the individual will eventually end up with very high levels of these amino acids. Ultimately, this will cause deterioration of brain cells and, in time, death if not treated. Thank god Harrison has shown no signs of discomfort and he doesn’t even realize we put him on a special diet that limits those 3 amino acids. He is so cute and I only just met him. I have hope though. I know Harrison will pull through.

Harrison!!!

Blog 2:
Guess what!!!! I am an older brother. I am so excited! However, my brother was diagnosed with Maple Syrup Urine Disease. My first reaction was “Yummy” and “what is that?” So my mom explained and it is not so good. I thought my brother could make maple syrup and my Mom would not have to spend money on Aunt Jemima’s. Just kidding! But that would be pretty cool. My Mom was really upset and it was hard for her to tell me the truth. Since I was the oldest, she thought I could handle the information. She told me that within the first 24 hours of Harrison’s, my new younger brother, birth, they took a “Plasma Amino acid blood test” from him. She said it is when blood is taken from the heel and is sent to the lab to determine the amino acid levels in the blood. He was positive for the disease and if it doesn’t get treated he could die really soon. I didn’t really get what was happening, but my mom told me she had been expecting this to happen because of our family history. My father and my mother are both carriers of Maple Syrup Urine Disease so it was likely that one child would receive the gene. Then she started describing the disease, but I didn’t understand half of what she said. This disease is something that is very rare. My mom said 1 out of 185,000 people get it. I asked her why that was and here is where I got confused. To quote my mom quoting the doctor “This disease is an autosomal recessive disease. For a child to get the disease he or she must inherit a defective copy of the gene from each parent. If both parents carry the MSUD gene, each of their children has a 25 percent chance of getting the disorder, and a 50 percent chance of being a carrier.” She said that since she knew I wanted a younger brother, it was worth the risk even though there was a very good chance Harrison could get it.

Waiting for the Baby

Blog 1:
From the perspective of a 12 year old boy whose mother has just given birth to a child who has Maple Syrup Urine Disease (MSUD)

My Mom has been pregnant for a long time and I just want her to have her baby. She gained a bit of weight, but I still think she looks pretty. My Daddy told me that I only needed to wait one more week until she would give birth to a boy. I always wanted a little brother. I have two annoying little sisters. Abby is 6 and Katie is 3. They always want to do girly things with me like dress up their dolls and talk about Dora the Explorer. I would way rather watch Sport Center to tell you the truth. My Mommy wants me to play with them and I would do anything to make her happy. But I am a pretty busy kid right now because I am preparing to have the best younger brother who I can play baseball and tennis with. He is going to be awesome, but I need to make a good impression. I want him to think I am cool. I don’t have much to say so I will keep in touch and write again in another week. Can’t wait!!! Oh yeah… I forgot to mention that I am Jack. Talk soon. Bye!