Question

Adapted from “Case Studies in Immunology” 7^th ed. by R. Geha and L. Notarangelo

THE CASE OF MICHAEL HENCHARD:

Near death in infancy as a result of invasive bacterial infection

Michael Henchard, the first son of a 25-year-old healthy mother, was born after 38 weeks’ gestation. He remained in the nursery for 3 days, with no complications, and was then discharged and sent home. After 2 weeks, during which he fed and grew well, his mother noticed a slight redness around the stump of his umbilical cord. She did not think much of it at first, but after 24 hours the redness had spread, and the umbilical area had become hard and swollen. Michael became very irritable, refused to nurse, and developed a fever (38.7^oC).

His mother took him to the pediatrician, who diagnosed Michael with omphalitis (an infection of the umbilical stump) and immediately referred him for treatment at the nearest emergency room. On arrival there, Michael was lethargic and hypotonic. His temperature was 40.2^oC and his heart rate above 180 beats per minute. His breathing was fast and shallow, and his blood pressure was low (60/35 mmHg). His abdomen was distended, and the abdominal wall was very warm to the touch, hard and erythematous (reddened).

The emergency room team immediately placed a venous catheter and treated Michael with fluids and broad-spectrum antibiotics. Blood cultures and a peri-umbilical swab were performed to identify pathogens. A complete blood count revealed severe neutropenia with an absolute neutrophil count (ANC) of 174 neutrophils µl^-1. Abundant Gram-positive cocci, identified as Staphylococcus aureus, were cultured from the umbilical stump swab as well as from the blood.

Michael was transferred to intensive care, where he remained for almost 2 weeks. He was treated with the antibiotic vancomycin, and with fluids and other medication to support his cardiovascular system. His condition gradually improved and the symptoms of infection in the umbilical area subsided. Nevertheless, his neutrophil count remained very low. His physicians therefore wondered whether his neutropenia was secondary to the infection (that is, due to bone marrow suppression) or whether he suffered from congenital neutropenia. To address this question, a bone marrow aspirate was performed. This showed normal numbers of granulocyte progenitors but a severe block in neutrophil differentiation at the promyelocyte stage and an almost complete lack of more mature forms. This suggested a diagnosis of severe congenital neutropenia (SCN).

2. What is the most commonly mutated gene found in patients with SCN?

3. What is the normal reference range for neutrophils in a complete blood count (number, not percent)? What is the threshold for qualifying as severe neutropenia? What is the normal function of neutrophils?

4. Which of the cardinal signs of inflammation was Michael displaying?

5. What is one potential long-term complication for patients with this disorder?

Answer 1

2) SCN is an autosomal recessive disorder caused by mutation in HAX1 gene which codes for mitochondrial protein.

3) normal reference range- 3000-7000/mm3

Threshold for severe neutropenia- less than 500/ mm3

Function- evades and engulfs foreign organisms, acts as phagocytic cell.

​​​​​​4) The cardinal signs which michael displayed are -

Redness in the umbilical region.

Swelling over umbilical region.

Fever

Increased temperature.

5) complication- acute myeloid leukaemis and myelodisplastic syndrome.