Directed Case Study:
The Death of Baby Pierre - A Genetic Mystery

by Clyde Freeman Herreid
University at Buffalo, State University of New York

INTRODUCTION

Case studies used in business schools are typically dilemma or decision cases where a business manager is faced with a problem which must be solved. The students' job is to analyze the problem and come up with possible options and solutions to the problem. There is no one answer to the problem in good cases. The discussion is necessarily open-ended.

Case studies used in teaching medicine also are generally dilemma cases where a physician must diagnose an illness and prescribe a treatment. But unlike the business case, there usually is a right single answer. So the case analysis is focused upon discovering the nature of that problem. The discussion is necessarily closed-ended.

In designing cases for science courses, both closed and open-ended cases may be desirable. If it is facts and principles that you are after as an instructor, then closed-ended cases may be preferable.

One of the most useful case study methods of the closed-ended type is the directed case study. Here a story is written and given to the students along with a number of questions about the case. The questions are structured to elicit answers which expose general principles. William Cliff and Ann Wright have written about their use of this method in the teaching of human anatomy and physiology (Advances in Physiology Education vol. 15(l): 519-528, 1996).

Below I have given a version of a directed case study. I used this genetics case in an exam for a course in general biology. It can be usefully employed in the middle of a lecture as suggested by Eric Mazur's concept quizzes. The case is based on an article by Jared Diamond entitled "Founding Fathers and Mothers" in Natural History magazine in June 1988 (see pp. 10, 12-15). The field of genetics is filled with interesting cases; and there is another example of a directed case in our collection, the famous case of hemophilia as it spread throughout Europe's royal families (Hemophilia, the Royal Disease).

THE DEATH OF BABY PIERRE
by Clyde Freeman Herreid
SUNY/Buffalo

On March 7, 1964, the baby known as Pierre was born in a remote part of Quebec Province in Canada. He appeared to be a healthy six-pound twelve-ounce child, except he did not eat well. Over the weeks after his birth, he became progressively more lethargic, vomiting periodically. Most peculiarly, his urine smelled of rotten cabbage, and soon the smell permeated his clothes and body. By the time he was admitted to the hospital on September 14, his muscles were weak and his ribs were showing. Baby Pierre had only gained half a pound in the six months since his birth. The doctors kept him alive by feeding him through a tube threaded through his nose and into his stomach. He gained weight and strength for a while, then suddenly took a turn for the worse. On November 30, baby Pierre vomited blood and died.

It soon became increasingly apparent that other babies in the Chicoutimi area of Quebec Province had similar symptoms, and people recalled similar deaths in this remote area 120 miles north of Quebec City. Some families lost several children to Pierre's disease. In those families stricken, it soon became clear that the parents were normal, but about one quarter of their children were afflicted. Boys and girls were equally afflicted. Specialists soon concluded that all of the facts indicated that this was a genetic disorder.



  1. If a genetic disorder was the cause, which answer is most likely correct?

    Explain the reason for your choice.







    (To be answered after Part 1 is handed in)

    Baby Pierre and the other stricken children were victims of hereditary tyrosinemia. This is caused by an autosomal recessive disease. The children lacked the normal gene which produces a liver enzyme that breaks down the amino acid tyrosine. Without the enzyme, tyrosine builds up in the liver and kidneys leading to the cabbage-like smell of the urine. Lethal side-effects follow. (A liver transplant is the only long-term treatment of the disease as of 1997.)

    Both parents avoid this fate because, although they carry one copy of the defective gene, they carry a normal gene which produces more than enough enzyme for normal liver function. The parents are unwitting carriers of the disease. In genetic terminology they are heterozygotes, while Baby Pierre was a homozygous recessive.

    Below is a pedigree of three generations of Canadians.



  2. Using the symbols of "a" for recessive allele and "A" for the dominant normal allele write the genotype for the following individuals.



  3. Is the above pedigree consistent with a sex-linked trait?




  4. What is the likelihood that female K will have a normal child if she marries a normal person who is a carrier for tyrosinemia?




  5. What is the likelihood of female K having a normal child if she marries her cousin M?




    Hereditary tyrosinemia is usually quite rare, affecting only 1 in 100,000 newborns. The situation in the French Canadians in Chicoutimi, Quebec, is dramatically different; 1 birth in 685 can be expected to produce a child with the disorder.


  6. From the answers below, what is the most likely reason for the large number of tyrosinemia cases in Chicoutimi. Explain the reason for your answer.

    Reason for your choice:







  7. The Hardy-Weinberg equation allows us to make some calculations about the local population.