Case Study Section 4 â Nitrogen Metabolism Based on âA Sickeningly Sweet Baby Boy: A Case Study on Autosomal Recessive Inheritanceâ by Jacqueline Washington and Anne Zayaitz (National Center for Case Study Teaching in Science) The Patient: Mathew Miller is a 7-day-old infant that is rushed to the emergency room by his parents Emma and Jacob Miller, Mennonites from Lancaster County, PA. Emmaâs pregnancy and delivery with Mathew was normal but he started having trouble nursing and now has completely stopped feeding. By the time they reach the emergency room Mathewâs limbs were rigid and he had had a seizure. The initial examination showed no infection and his x-rays were normal. The family history collected by the Doctor revealed that Emma and Jacob had had a previous son, Samuel that died at 9 days-of-age. There also is a history of unexplained childhood mortality on both sides of the family; Emmaâs mother had two sisters who died in the first year of their lives and Jacobâs father had a sister who died at 7 months of age. Emma also points out to the Doctor that Mathewâs diaper has a funny smell to it. Blood and urine samples were taken for testing and skin biopsies from Mathew, Emma, and Jacob were taken and tested for enzyme activity. The tests results showed that:
⢠Mathewâs urine had elevated levels of the branched chain amino acids and their α-keto acid derivatives (which caused the sweet smell in his diapers)
⢠Both Emma and Jacobâs skin biopsies had nearly normal levels of branched chain amino acid metabolism/enzyme activity
⢠Mathewâs enzyme activity was less than 2% of normal
Question 1: What is the most likely diagnosis for Mathew?
A. Argininemia
B. Diabetes mellitus '
C. Maple syrup urine disease
D. Phenylketonuria
Question2: What enzyme did the skin biopsy test measure?
A. Carbamoyl phosphate synthetase I
B. Alanine aminotransferase
C. Phenylalanine hydroxylase
D. Branched-chain α-keto acid dehydrogenase complex
Question 3: This enzyme functions VERY similarly to two other enzymes that we have discussed, what are they?
A. Phosphofructokinase-1 and fructose 1,6-bisphosphatase (FBPAse-1)
B. Pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex
C. Urease and arginase
D. Isocitrate dehydrogenase and malate dehydrogenase
Question 4: How did Mathew (and presumably Samuel) inherit the disease if both Emma and Jacob have normal enzyme activity levels?
A. Emma and Jacob must both be carriers for the disease but their one normal gene is enough to maintain enzyme activity levels.
B. The disease can happen spontaneously, there is no genetic link.
C. Jacob is not really the father of the boys.
D. The disease can skip generations.
Question 5: What would be the best diet for Mathew to follow to control his disease?
A. Atkinâs diet (low carbohydrates, high fat, and high protein)
B. Low protein
C. Low fat
D. No special diet will control the disease
Over the next 4 years Mathewâs metabolic disease is controlled by his special diet but he still suffers approximately 3 metabolic crises a year. These occur when amino acids accumulate in his blood leading to the swelling of his brain. Even something as simple as a cold or the flu can affect his amino acid levels and send his metabolism into crisis. Jacob and Emma decide that âWe cannot continue to live in constant fear that a minor infection or a simple cold or ear infection could kill our son. Even though we are doing everything we are supposed to, he is still getting sick and we are afraid we may lose Mathew.â They learn that some children with Mathewâs disease have undergone liver transplants and are effectively cured.
Question 6: How/why would a liver transplant effectively cure Mathewâs condition?
A. A new liver would be able to spread itâs genes throughout the body and correct the genetic disorder.
B. A new liver would more effectively respond to metabolic hormonal control.
C. A new liver would express the functional enzyme needed to metabolize the amino acids causing Mathewâs condition.
D. A new liver would produce more hemoglobin to transport oxygen more effectively.
The family is directed to Dr. Morton of Childrenâs Hospital of Pittsburgh, where transplant experts agree to list Mathew for a liver transplant. Jacob and Emma learn that children who receive a liver transplant have to take strong immunosuppressive drugs for the rest of their lives. It was also clear that there was a 40% possibility that Mathew could reject the liver and need a second transplant (which also might be rejected) or he could die from surgical complications.
Question 7: Assuming the liver transplant was successful and Mathew did not reject the new liver, what type of diet would Mathew be able to/need to eat?
A. He would still need to eat his special diet but he would be at less risk of a metabolic crisis
B. He could eat a normal diet
C. He would need to change to a high protein diet like Atkinâs
D. He would be on an all liquid diet
Question 8: Emma and Jacob decide they want to try to have another child. What would be the chance that this child would also have the disorder that Mathew and Samuel have/had?
A. 0 %
B. 25%
C. 50%
D. 75%
E. 100%
Question 9: If Mathew grew up, got married, and decided to have children, what would be the chance that his children would have the disorder? A. 0%, the liver transplant would have cured him
B. 25%
C. 50%
D. 100%
E. It would depend on his wife, if she was normal than there would be a 0% chance of his children having the disorder but 100% would be carriers, if she was a carrier than there would be a 50% chance of his children having the disorder and a 50% chance that they would be a carrier.
Question 10: The disorder is found in 1 in 200,000 infants throughout the US but 1 in 200 in the Amish and Mennonites of Lancaster County, PA. Why is there such a difference in the prevalence of the disease?
A. There are environmental factors associated with being Amish or Mennonites that increase the prevalence.
B. There is a large amount of genetic similarity within these populations because they tend to marry within the population so recessive disorders such as this are more likely.
C. The gene mutation is preferentially carried in Caucasians so when you average the prevalence across all races in the US the prevalence drops.
D. It is unknown why the prevalence is so much greater in Amish and Mennonites.
