Section: IntroductionOverall Progress: 20%

Chapter 1. Sudden Onset: An Introduction to Metabolism

Sudden Onset: An
Introduction to Metabolism

By Justin Hines, Lafayette College

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Makali slept. His mother held his hand, staring intently at his face, breaking only to wipe away tears. It was nearly midnight and quiet in the hospital. Makali’s father was in the hallway, pacing. Other than his occasional muscle spasms, and hand tremors that didn’t interfere with his day-to-day life, Makali had been a happy and healthy teenager. Now, no one understood what was happening to him . . . and that was terrifying for his parents. Moving to the United States had always been a dream for the family, but the last 24 hours had been a nightmare of vomiting and diarrhea. His mother’s thoughts turned to her parents and she shuddered. Had the curse of the Fore people been passed on to her children? Given the family’s tragic history, she feared the worst and sobbed . . .

You are a biochemist who is working with a group of physicians. It is up to you to determine what is wrong with Makali by systematically investigating this case. Are you up to the challenge?

About this case

In addition to reviewing some interesting and important aspects of human biochemistry, this case is meant to help you understand the mechanics of the remaining case studies in this collection. You may have free access to both your textbook and the Internet while you solve these cases, but please remember that a critical aspect of these cases is that you are meant to learn and review fundamental biochemistry concepts by thinking critically about the data presented in each case and by reviewing the relevant sections in your textbook. You are NOT to “guess” the correct disease, and we have taken great care to avoid obvious answers that can be revealed by a simple search of the Web for key terms.

In these cases, you will be placed in the shoes of someone who is investigating the case and you will have many investigation options, including tests for specific metabolites and tests to examine the activity of specific enzymes. However, it will typically be far more efficient for you to focus first on more general “information gathering” options than to immediately begin guessing and testing poorly formulated hypotheses by choosing specific tests. Therefore, we strongly suggest that you begin your investigation by gathering more information about Makali and his condition. As you will see in these cases, some investigations will open up new investigative directions and options, which may lead either to critical clues or to dead ends. It is up to you explore the case and find out! Get started by making your first choice from the options shown on the following page.

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INFORMATION-GATHERING INVESTIGATIONS

Click to select any option in any order.

Conduct a blood test for common poisons or narcotics.

Results: No poisons or narcotics were found.

Conduct a fecal analysis to look for blood and intestinal parasites.

Results: No blood or intestinal parasites were found.

Determine the blood serum concentration of glucose.

Results: [Glc] = 95 mg/dL (normal range: 70–110 mg/dL)

Determine the blood serum concentration of galactose.

Results: [Gal] = 1.5 mg/dL (normal range: 0–6.0 mg/dL)

Determine the blood serum concentration of H3O+ ions (blood pH).

Results: pH = 7.4 (normal range: 7.35–7.45)

Evaluate overall physical appearance, including the presence of insect bites or other injuries.

Results: The subject is a young, adult male with a slim, athletic frame but otherwise appears normal. No insect bites or other injuries are present.

Examine hair for common toxic compounds (heavy metals and narcotics).

Results: Levels of common heavy metals were normal and no narcotics were found.

true
true

Interview Makali’s parents to ask about the “family history.”

Results: Makali and his parents had recently emigrated from the highlands of Papua New Guinea. His family is part of the famous Fore tribe; after living in the tribe for most of their lives, they decided to give Makali a different life in the United States. His mother starts to cry as she recalls that both her parents died in the Kuru epidemic that made the tribe famous and she is terrified that he might be coming down with Kuru. His father interjects to say that it is not possible and that he is far more concerned that Makali has some other infectious disease to which he had never previously been exposed. For example, he says, Makali had a severe allergic reaction to the tetanus/pertussis booster shot as a child and so he has been unable to be re-vaccinated as an adult (for fear that he may go into anaphylactic shock). Therefore, Makali may be susceptible to whooping cough (pertussis). This wouldn’t have been a concern 10 years ago, but vaccination rates for whooping cough are plummeting in the United States, eliminating herd immunity in some areas, and so the disease is returning. Ironically, vaccination rates in the Fore tribe are much higher than in the United States, so Makali’s parents had concerns about coming to the United States, which is falling behind in this area of basic medical care!

The doctor you are working with says that checking immunoglobulin (Ig) levels should reveal if there is a serious infection. He also points out that Kuru does not cause Ig levels to rise. If Makali does have Kuru, then it may require a brain biopsy to diagnose it for certain.

You now have the following two new investigation options available to you:

Test common immunoglobulin (IgG, IgA, IgM) levels in the blood for signs of an infection.

Results: All values are in normal ranges (normal ranges: [IgG] = 560–1800 mg/dL; [IgM] = 45–250 mg/dL; [IgA] = 100–400 mg/dL).

Conduct a brain biopsy.

Results: Rejected! The physicians you work with tell you that there is not enough evidence yet that Makali has Kuru to justify a highly invasive and dangerous procedure like a brain biopsy. You should continue to gather more evidence about this case and perhaps this investigation will be justified in the future.

true
true

Interview one of Makali’s friends to ask about the day he first became sick.

Results: Makali became sick after eating with friends at a pizza place. He ate pepperoni and cheese pizza, and had a vanilla milkshake and an ice cream sundae (a banana split). Apparently, Makali had never tried ice cream before coming to the United States; he had a taste of it for the first time at this same restaurant about a week ago, and this was the first time he’d been back. It was also his first time eating pizza.

Makali’s friend mentioned something about his diet; you could ask his parents more about this specifically. The following is now a new investigation option:

Ask Makali’s parents more about his diet.

Makali primarily ate his mother’s cooking at home, mostly rice, beans, and taro. Because of the fear that his parents might have been exposed to Kuru, which can incubate for more than 50 years without symptoms, and because Kuru can theoretically be passed from person to person in breast milk, Makali was never breast-fed. He had gotten sick as a baby and since then had neither liked nor drank goat’s milk nor has he eaten goat cheese, both abundant in Papua New Guinea. Rather he has been very fond of coconuts and bananas since he was an infant.

Makali’s illness seems to be closely related to the consumption of dairy products. Review section 16.3 of Tymozcko, Biochemistry: A Short Course, 3rd ed., for information relating to the consumption of dairy products, carbohydrate metabolism, and health issues before proceeding. Then, when you are ready to answer questions about this topic, proceed by clicking the link below:

Continue to assessment questions.

1.

Which of the following are health issues relating to both carbohydrate metabolism and the consumption of dairy products that are discussed in Section 16.3 of Tymozcko, Biochemistry: A Short Course, 3rd ed.

A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
K.

10
Correct.
Incorrect.
true

1

You now have the following four new investigation options available to you:

Conduct a lactose intolerance test on Makali.

Results: Request denied. The doctors you are working with remind you that if we have not yet ruled out galactosemia for certain, a lactose intolerance test could be very dangerous for Makali

Test the activity of the enzyme aldolase.

Results: [Aldolase] = 3.0 U/mL (normal range: 0–7.0 U/mL)

Test the activity of the enzyme galactose-1-phosphate uridyltransferase (GALT).

Results: [GALT] = 4.0 U/g Hb (normal range: 18.5–28.5 U/g Hb)

Testing for the activity of the enzyme galactose-1-phosphate uridyltransferase (GALT) in the blood is the most common and accurate test for the most common form of galactosemia, simply called “type 1 galactosemia.”

8.

What reaction does this enzyme catalyze?

A.
B.
C.
D.
E.

4
Correct.
Incorrect.
true

Test the activity of the enzyme lactate dehydrogenase (LDH).

Results: [LDH] = 160 U/L (normal range: 110–210 U/L)

Investigate medical history including current medications.

Results: Makali’s parents report that he is not on any medications currently, and, as far as they know, he has never used illegal drugs. They note his occasional muscle spasms and his constant hand tremors, but they say he has suffered from these all his life, not just since becoming ill. They note that he was sick as a baby (jaundice, diarrhea, and vomiting), but he recovered quickly and has been in general good health ever since. They also note that he has always had poor eyesight since childhood, but it’s not an issue they’ve ever looked into.

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Congratulations on completing this Case Study! The following Case Summary gives a full explanation of the murder of Dr. John Bleu.

About this case: A debriefing

We hope that you enjoyed investigating this case and learning about a common inborn error of metabolism. As you work on additional case activities in the future, you will again have access to both your textbook and the Internet, but please remember that you should not simply guess the correct answer since getting to the correct answer is not necessarily the point of these cases. Rather, you are meant to learn and review fundamental biochemistry concepts by thinking critically about the data presented in each case, and by reviewing the relevant sections in your textbook. Trying to use Web searches of key terms to guess the answer may in fact lead you astray. For example, in the current case, you immediately learned that Makali is a member of the Fore (Makali is a traditional name of this group). A quick search of the term “Fore people” may have led you to jump to the conclusion that Makali is suffering from Kuru, the disease that made the Fore known to the rest of the world. This conclusion is a red herring, not at all supported by the details given in the case. Be sure to avoid trying to find a shortcut to the solution of future cases in this manner and remember that you should evaluate all the facts of the case as they are presented.

These cases are intended as learning tools, not evaluations. Preferably, we’d like them to be enjoyable too! We hope that in working each case you will enhance your understanding of biochemistry and your integration of biochemical information. Knowing the answer in advance only hinders your own learning, and likewise you do a disservice to others if you “spoil” the case for them. It also takes all the fun out of the activity since no one likes spoilers. Once you complete a case, please keep the answers to yourself and please don’t spoil the fun and the learning opportunity for others!