Question

I. Case Study Mr. and Mrs. Vanderveer owned a farm in the Hudson Valley in lower New York State. They were both descended from Dutch settlers who came to Hudson Valley in the mid-17th century. There were multiple consanguineous marriages among their ancestors, and Mr. and Mrs. Vanderveer were distantly related to each other. At the time of this case, they had five children- three girls and two boys. Their youngest daughter, Susan, was 10 months old when she developed a cold, which lasted for 2 weeks. On the 14th day of her upper respiratory infection, she became sleepy and felt very warm. Her mother found that her temperature was 41.7°C. When Susan developed convulsive movements of her extremities, she was rushed to the emergency room but she died on the way to the hospital. Post-mortem cultures of blood were obtained, and also from her throat and cerebrospinal fluid. All the cultures grew Hemophilus influenza, type b. At autopsy Susan was found to have no spleen. At the time of Susan’s death her 3-year old sister, Betsy, also had a fever, of 38.9°C. She complained of an earache, and her eardrums were found to be red. She had no other complaints and no other abnormalities were detected on physical examination. Her white blood count was 28, 5000 cells/µl (very elevated). Cultures from her nose, throat, and blood grew out H. influenzae, type b. She was given ampicillin intravenously for 10 days in the hospital and was then sent home in good health. Her cultures were negative at the time of discharge from the hospital. She was seen by a pediatrician on three occasions during the following year for otitis media (inflammation of the middle ear), pneumonia, and mastoiditis (inflammation of the mastoid bone behind the ear). David, Susan’s 5-year old brother, had been admitted to the hospital at 21 months of age with meningitis caused by Streptococcus pneumoniae. He had responded well to antibiotic therapy and had been discharged. Another occurrence of pneumococcal meningitis at 27 months of age had also been followed by an uneventful recovery after antibiotics. He had had pneumonia at age 3 ½ years. At the time of Susan’s death he was well. The two other children of the Vanderveers, a girl aged 8 years and a newborn male, were in good health. All the Vanderveer children had received routine immunization at ages, 2, 4 and 6 months with tetanus and diphtheria toxoids and killed Bordetella pertussis to protect against tetanus, diphtheria, and whooping cough, which are three potentially fatal diseases caused by bacterial toxins. All of the Vanderveer children had protective antibody responses against these antigens, indicating a normal immune response against T-dependent antigens. However, when they were immunized with polysaccharide vaccine against S. pneumoniae that contains capsular antigens from 23 distinct strains of S. pneumoniae, neither David not Betsy were able to mount a good antibody response, whereas their two healthy siblings did. This indicated Betsy and David had a defect in mounting antibody responses against polysaccharide antigens. All of the children and their parents were injected intravenously with radioactive colloidal gold (198Au), which is taken up by the reticuloendothelial cells of the liver and spleen within 15 minutes after the injection. A scintillation counter then scans the abdomen for radioactive gold. The pattern of scintillation is shown in

Figure 5.

Figure 5: A scintillation scan of the abdomen after intravenous injection with radioactive colloidal gold (¹⁹⁸Au). The top most scan is from Betsy’s mother. The middle one is from Betsy and the lower most scan is from David.

Questions: 1. What do you observe on the scintillation scan?

2. Explain your observations in Q1. In other words, what is going on with this family?

3. What diagnostic procedures did they use to diagnose Susan’s case?

4. Why were the white blood cell counts elevated in Betsy?

5. Nicholas Biddleboy, a 5-year old boy, has had his spleen removed after sledding accident, during which both he and his sled struck a tree trunk. In the emergency room of a nearby hospital, it was determined that his spleen had been ruptured. The surgeon, after removal of spleen that had indeed ruptured, call you for an immunology consultation. What do you advise?

6. On one of the check-ups, David complained of swollen/painful tonsils. What could be the possible reasons?

7. Next page: The Vanderveer family is unique in the medical literature. The parents, who were distantly related, were normal and had normal spleens. Five of their eight children were born without spleens. Of these, only Betsy subsequently had children – four boys an done girl. They are all normal and have spleens. What is the inheritance pattern of congenitial asplenia (an autosomal recessive disorder) in this family? According to Mandelian laws how many of the eight Vanderveer children would be expected to have no spleen?

Answer 1

3. Susan undergone autopsy and found to be having no spleen

Her blood, Throat and cerebrospinal fluid showed positive for Hemophillus influenza.

4. Betsy white blood call count increased because she had severe otitis.

5. Post splenectomy immunology consultation is required because there will be a decreased immune response to encapsulated bacteria S. pneumonia, M meningitis, H influenza type n. So immunization is required to prevent post splenwctomy infection.

6. David complained of painful tonsils because he would have acquired tonsillitis as they were having a defect in mounting antibody against polysaccharide antigens of S. pneumonia.