The signs and symptoms were difficult and confusing, even scary. The infant developed a rash and a skin abscess. He ate but kept losing weight. His parents were scared.
Specialist after specialist in his native Guatemala examined him. No one could figure out his condition, but everyone agreed on one thing:
Joaquin was very sick.
As the baby approached 3 months old, a consensus formed that his parents — Andy and Luisa — should take him to the United States for specialized medical care. Luisa’s father is a Guatemalan surgeon who knew someone who might be able to help.
Roberto Sosa, M.D., is a Guatemala native who has practiced medicine at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, for nearly five decades. A neonatologist by training, he established the hospital’s neonatal intensive care unit in 1976. Sosa has cultivated international relationships over the years, particularly in Central America and the Caribbean.
As Sosa made arrangements for Joaquin in St. Petersburg, Andy and Luisa had to scramble. Guatemala generally takes a month to issue a visa, but Joaquin got his the same day.
“That never happens in Guatemala,” Andy says. “That was the first miracle, the first door that opened to us. We managed to leave the next day. Time was against us, and that helped us get to the hospital in time to save his life.”
Infant in Peril
The family arrived in St. Petersburg three days before Joaquin’s scheduled appointment, but his condition was declining, so they arranged to move the appointment up by a day. When pediatrician Heinz Chavez saw Joaquin’s condition, he immediately directed them to the pediatric intensive care unit. Joaquin was dehydrated, and his blood sodium level was very high, which can be fatal.
“It was sad,” says critical care medicine specialist Allison Fahy, describing Joaquin’s condition upon arrival. “He was critically ill and malnourished. It was definitely a long night, but the family was super nice and always lovely. I’m glad we were able to stabilize him.”
When Joaquin was referred to Johns Hopkins All Children’s, the best theory was that his problem might be a condition called hyper IgE syndrome, a group of rare genetic disorders characterized by an elevated level of immunoglobulin E (IgE), a type of antibody rising with severe allergies but also linked to severe disorder of the immune system.
Specialists from several disciplines, including allergy and immunology, gastroenterology, clinical genetics, infectious disease and others, cared for Joaquin to conquer the threats of his hyperactive immune system that could not fight infections but caused systemic inflammation. Inflammation is a natural body response to infection or injury, but Joaquin’s was severe and seemed unregulated.
The medical team ruled out hyperIgEsyndrome and within about two weeks concluded Joaquin’s condition was Omenn syndrome, a rare life-threatening immune system emergency normally associated with overt inflammation in severe combined immunodeficiency (SCID). Typically, Omenn syndrome is treated with brief but harsh immune modulation shortly followed by hematopoietic stem cell (bone marrow) transplant, but as researchers and clinicians have learned more about the condition, they have seen forms that can be managed in other ways.
“Initially, Omenn syndrome was only ascribed to patients who have SCID with bone marrow cell abnormality and you have to do a bone marrow transplant,” says Jolan Walter, M.D., Ph.D., division chief of the University of South Florida and Johns Hopkins All Children’s Pediatric Allergy & Immunology program. “But recently, we are finding a milder form of Omenn syndrome in patients, especially among those with a profound defect of the thymus, a gland where the essential immune T cells mature. Omenn syndrome with underlying genetic root cause is a very important diagnosis to make. It is a fatal disease unless treated first for severe inflammation and second for the underlying cause.”
Omenn Syndrome Expertise
Walter, also director of the Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies at Johns Hopkins All Children’s, is internationally recognized for expertise in primary immune deficiencies and other immunology conditions, including SCID and its variant Omenn syndrome.
During her fellowship at Harvard University and Boston Children’s Hospital, she trained with Luigi Notarangelo, M.D., who was the first researcher in 1998 to publish in the journal Cell the root-cause of Omenn syndrome, a previously enigmatic form of combined immune deficiency. Walter worked with patients and mouse models of Omenn syndrome at Harvard and has been researching the condition for 15 years. She is part of an international collaboration that has a registry of 130 Omenn syndrome cases from North America and Europe.
Walter recognized the signs of Omenn syndrome early on in Joaquin.
“I remember seeing Luisa for the first time holding her baby, and looking at him, I realized that this is not hyper IgE syndrome,” she says. “This was something more severe, and we had this feeling it might be Omenn syndrome that was atypical in many ways.”
Although Omenn syndrome often is treated with a bone marrow transplant, Walter recognized that wasn’t the right course for Joaquin. He was producing the stem cells needed to develop his immune system.
But they weren’t developing to the best effect.
A Thymus Deficiency
White blood cells called “T cells” that are developed from bone marrow stem cells are a key to the immune system. Immature T cells migrate to the thymus, a gland located in the upper chest behind the sternum and between the lungs. It generally is right in front of the heart.
Essentially, the thymus trains T cells to distinguish harmless proteins made by the body from dangerous pathogens and fully diversify them to fight any infection that a human may encounter.
Walter recognized that Joaquin was releasing cells from the bone marrow, so he didn’t need a stem cell or bone marrow transplant. It was the lack of an effective thymus that was the problem.
“We had to differentiate the two problems,” Walter says. “He actually could make some good T cells. Some of them were able to react to different infections, and he created a nice diversity of the T cells, but some of the T cells became rogue and started to cause inflammation, including a severe rash and gut inflammation.”
Walter drew from her prior studies and consulted experts around the world (John Sleasman, M.D., at Duke; Austen Worth, BM BCh, Ph.D., and Alexandra Kreins, M.D., Ph.D., in London; and Notarangelo, now at the National Institutes of Health in Bethesda, Maryland) about how to manage Joaquin’s Omenn syndrome condition. They adopted a process called immunomodulation, which carefully alters the body’s immune system through the use of anti-inflammatories, steroids and other medications along with support of antibiotics and immunoglobulin to support the patient’s ability to fight infection.
“He had a very interesting course because he got better and then he got worse, so there were a lot of ups and downs,” Walter says. “It was very hard decision-making every week. We had to pick our own battle about his feeding, his inflammation, his immune system and how best to support him.”
It took a village to help Joaquin, including the dedicated allergy immunology fellow trainees and faculty of Walter’s program. Their learning did not stop at the bedside, and often connected with the research laboratory team to fully understand how the “flames of the disease” are quieting down in Joaquin.
During his prolonged hospital stay of several months, Joaquin was surrounded by medical experts of all specialties and a loving family. His father, who played in a rock band during his youth, often jammed with Child Life support to bring a smile to the baby’s face.
Gradually, Joaquin improved. In January 2025, when he was 8 months old, he got to return home to Guatemala. Walter used her contacts through the Jeffrey Modell Foundation to find allergy and immunology specialist Rossina Duarte Ordoñez in Guatemala to see him regularly.
“Every week, I’m getting messages from the doctor, and the family is reaching out,” Walter says. “We are deciding about his medication. Nothing is decided about his treatment without input from our service here at Johns Hopkins All Children’s.”
The Road Ahead
Joaquin still has challenges. The family often wears a mask around him to avoid compromising his immune system. They seek a solution to allow him to both physically and socially flourish.
A thymus transplant might be a possibility even though it is offered at only a few places in the world. Walter is helping the family research and evaluate its options.
At a follow up visit to Johns Hopkins All Children’s just after his first birthday in April, Joaquin displayed a captivating smile at various locations, including a visit to Walter’s research lab.
Andy and Luisa are grateful to Walter and optimisticshe will find a solution. They know their son won’t give up.
“You could see in him a little warrior with great willingness to fight for his life, and I think that was very special,” Luisa says. “I always tell him he was born into a family of love, and that will save his life.
“When I look at his smile, I think that is the most wonderful gift that he can make us.”
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