Doctors at the Children’s Hospital of Philadelphia report the case of a baby with recurrent ear infections. The doctors diagnosed him with a new form of agammaglobulinemia: his body does not produce B lymphocytes, the source of antibodies.
- Doctors at the Children’s Hospital of Philadelphia have discovered a new form of rare disease in a 7-month-old baby with recurrent ear infections.
- Called mutated agammaglobulinemia PU.1, it results in a mutation of the PU.1 gene, which usually helps in the production of B lymphocytes, cells essential for the production of antibodies.
- The little boy was able to benefit from a bone marrow transplant from his older brother, which allowed him to eventually produce his own B lymphocytes.
Little Luke Terrio was around seven months old when his mum started to realize something was wrong. He constantly suffered from ear infections, had red spots on his face, and was tired all the time. His development was stagnating and the antibiotics given to treat his frequent infections were no longer working.
Followed by a doctor at the Children’s Hospital of Philadelphia (CHOP), he then had a series of blood tests which revealed that Luke had no antibodies. At first, specialists thought the little boy might have X-linked agammaglobulinemia, a rare immunodeficiency syndrome in children. However, as they continued to study Luke’s case, the CHOP research team realized that Luke’s disease was unlike any other illness previously described.
A very rare mutation of the SPI1 gene
Doctors used whole exome sequencing to analyze Luke’s DNA. They then discovered the genetic mutation responsible for his condition, which prevents Luke and patients like him from making B lymphocytes, and therefore antibodies to fight infections. In a study published in the Journal of Experimental Medicinethey explain that they have named this disease mutated agammaglobulinemia PU.1 (PU.MA).
“It can be quite scary for a family whose child has a mysterious illness, explains Neil D. Romberg, attending physician in CHOP’s Division of Allergy and Immunology, lead author of the paper. In this case, science has provided an explanation, thanks to many CHOP services. Understanding the cause of Luke’s condition has absolutely helped us know which direction to take his therapy.”
To identify the causative gene, CHOP researchers compared the whole exome sequences of 30 patients around the world born without B lymphocytes, the cells that produce antibodies. In this group, they identified six patients, including Luke, who had a mutation in a gene called SPI1, which codes for the protein PU.1. PU.1 helps B cells growing in the bone marrow to open “doors” in their chromatin, a very compact type of DNA. Without PU.1, these gates remain closed, and B cells never form. The six patients with PU.MA, whose age ranged from 15 months to 37 years, each had different SPI1 mutations but had in common insufficient levels of PU.1, absent B cells and, therefore, no antibodies. .
A beneficial bone marrow transplant
As Luke’s condition was entirely new, there was no guidance for his family or medical team to follow. After consulting with the research team, the family decided to have a bone marrow transplant in hopes the procedure would help them make their own B cells and antibodies. They soon discovered they had a perfect donor living under their own roof: Luke’s three-and-a-half-year-old older brother Jack.
The transplant managed to make Luke produce his own B cells until the latter were able to create enough protective antibodies on their own. For now, Luke continues to be protected against infections thanks to the antibody infusions he receives every two weeks. “We call them his ninjas, says Michelle, Luke’s mom, describing the antibodies. We tell him he doesn’t make his own ninjas so he needs these ninja infusions to fight germs and keep him safe.” Thanks to these “ninjas” and his brother’s bone marrow donation, Luke is now an energetic 4-year-old boy who loves Transformers, fire trucks and riding a balance bike.
.