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Source: Janet Basu
415-476-2557
02 July 1998
NAVAJOS TURN TO UCSF FOR BONE MARROW TRANSPLANTS FOR CHILDREN WITH GENETIC IMMUNODEFICIENCY DISEASE
It took only a few minutes for doctors in Tuba City, Arizona to diagnose four-month-old Chasity Neztsosie’s symptoms. Within half an hour they were on the phone with Morton J. Cowan, MD at Lucile Packard Children’s Health Services at the University of California San Francisco (UCSF). Chasity had been born with severe combined immunodeficiency disease (SCID).
Two days later Chasity and her mother took a medical evacuation flight to San Francisco for a mother-to-daughter transplant of healthy bone marrow stem cells. The bone marrow transplant is her chance to build a robust immune system to fight off infection.
It was lucky for Chasity that her parents had brought her home that week late in February to the Navajo Nation. In Las Vegas, where the little girl and her twin brother were born, doctors did not recognize Chasity's symptoms because SCID is very rare in the general U.S. population. But when her mother, Geneva Bighorse, brought the baby in to the Navajo Area Indian Health Service in Tuba City, health workers knew exactly what her frequent fevers, rashes and the ulcerating sores in her mouth might mean.
"The doctor told me right away that it might be SCID," Bighorse said. Chasity's father, Wilfred Neztsosie, said that it was both alarming and a relief to know the reason for their baby's recurrent illnesses.
Chasity was not the first baby to be rushed from Tuba City to UCSF for a bone marrow transplant. Over the past two decades, doctors in the Navajo Nation working with specialists from UCSF and elsewhere have identified a particular form of SCID as one of the most common potentially fatal birth defects among Navajos. Approximately two out of every 5,000 newborn Navajo babies have this genetic condition, according to Diana Hu, MD, acting maternal child health coordinator for the Indian Health Service in Tuba City. As many as two percent of the Navajo population may carry the defective gene that causes it.
That means SCID -- while still quite rare -- is as frequent in this small population as the most common potentially fatal birth defect in the general U.S. population, cystic fibrosis. In the general population, SCID occurs to about one of every 300,000 newborns.
In January, 1998, Cowan, Hu and their colleagues reported in the American Journal of Human Genetics that the same type of SCID that has struck Chasity and other Navajo babies also is found among the Apaches and a small group of Athabascan-speaking Native Americans from the Northwest Territories in Canada. They localized markers from a SCID-related gene that has been shared by members of these groups at least since 1300 AD.
Infants born with this type of SCID have an absence of circulating T cells and B cells and a severe impairment of T-cell function. With these parts of their immune systems missing, it is difficult to resist a variety of germs that normal children routinely handle with the body’s natural defense mechanisms. A newborn with SCID may develop fevers, diarrhea, pneumonia, and severe sores in the mouth and on the genitals. Typically the child does not thrive and grow as a normal baby would. A bone marrow transplant is the only available treatment.
Increased awareness and a quick response by Indian Health Service physicians are saving the lives of many of these SCID babies.
Chasity now is going home, nearly four months after her March 11 surgery to receive bone marrow stem cells from her mother. Bone marrow is the spongy material in the center of the bones; stem cells are the factories in the marrow that manufacture all the components of blood, including white cells that help fight infection.
UCSF has pioneered a type of bone marrow transplant for babies like Chasity, who do not have a relative with perfectly matched immune system markers: A parent who is a close match donates stem cells which are specially treated to make them suitable for transplant.
Chasity tolerated the procedure well, Cowan said. "Chasity was quite ill and emaciated when she arrived at UCSF," he said. "But she has responded nicely to treatment. She is developing and growing and we are optimistic that she will be cured of her immunodeficiency disease."
"So far everything is fine. I hope everything continues to go well for her," Bighorse said. "It's curable, that's the main thing."
Cowan directs the UCSF Pediatric Bone Marrow Transplant Division, a part of Lucile Packard Children’s Health Services and UCSF Stanford Health Care. The bone marrow transplant team is known for its interest and expertise in treating children with inherited immunodeficiency diseases. "We have diagnosed and treated close to 60 children with SCID from California and other western states and Canada," he said. "They all present with unique problems that we must solve. Overall, 80 percent of these children are cured with a transplant and live normal lives."
Over the past decade, Cowan has done extensive work among the Navajo and other related Native American populations to find the cause of the disease and to identify the best treatment.
The genetic defect responsible for SCID has not yet been determined. Working to hone in on the specific gene, Cowan and his colleagues recently discovered its approximate location on Chromosome 10. Once the gene is found, health workers will be able to do carrier testing and genetic counseling for the families of patients with SCID. Eventually, the researchers hope to develop an effective gene therapy to treat the disease in utero, before the baby is born. Currently, bone marrow transplantation is the only cure.
As a result of Cowan's work in Arizona, UCSF has become the major treatment center for Navajo children with SCID.
"We wanted to stick with something we knew was working well," said Hu, the doctor who initially sees the infants and who follows their care. "There are many special issues with Navajo kids and the UCSF team has been sensitive to the culture of these patients."
Since 1986, the UCSF Medical Center has performed bone marrow transplants on 13 infants with Chasity's type of SCID. Of those, 11 are alive and well.
Cowan has joined with Hu and other Indian Health Service workers who are getting the word out among families of Navajos and closely related tribes to look for symptoms in newborns that might indicate SCID. Someparents who have had SCID children have taken prenatal tests to determine if the next child may need treatment for the disease.
For the three and a half months since her transplant, Chasity and her mother have stayed in San Francisco, as the baby gains strength and her physicians watch for signs that her mother’s bone marrow has successfully engrafted. Bighorse and Neztsosie have been staying at Koret Family House near the hospital; Neztsosie has made frequent trips back and forth from Arizona to take care of family responsibilities. For one visit to San Francisco, he brought Chasity's grandmother, her twin and her two big brothers.
"Chasity is doing pretty good now," Neztsosie said. "She's starting to gain weight, and that's our main goal now. We appreciate all the doctors and nurses and social workers who have helped us through this."
Bighorse echoed his thanks. She has been working with the special equipment that she will need to administer medications and extra nutrients during the first few months that Chasity is home. "Everything has gone well here," Bighorse said, "But at this point, we're all looking forward to going home."
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