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Stanford Report, March 19, 2003

New Packard laboratory speeds diagnosis, treatment of genetic defects With rapid response, some diseases can be blunted


Each baby born at the Lucile Packard Children’s Hospital’s Johnson Center gets the same rude welcome: a heel prick to obtain a blood sample to screen for four dangerous genetic diseases.

The infant’s brief scream that accompanies this tough love is bearable because in this case, knowledge is power. Without prompt diagnosis and treatment, the diseases can cause mental retardation and life-threatening illness.

The new Biochemical Genetics Laboratory at the hospital rapidly analyzes samples from newborns who test positive for any of the diseases included in the screen, as well as from older children or adolescents who have begun to exhibit suspicious symptoms such as vomiting, lethargy or seizures. It has recently begun to accept samples from surrounding hospitals, practice groups, laboratories and community physicians.

Tina Cowan is leading a charge to rapidly diagnose certain genetic diseases in newborns. Her efforts could save lives and prevent severe illness by allowing doctors to treat diseases before symptoms occur. Photo: Krista Conger

"Unless you test for specific diseases, you won’t know what you are dealing with," said laboratory director Tina Cowan, PhD. "And a positive result on a screen does no good if you can’t confirm it."

The lab, which is the only one of its kind in Northern California, eliminates the lag time of at least a week that once confronted parents and physicians when samples were sent to laboratories scattered across the country for analysis.

Cowan also offers more personalized service than her distant counterparts.

"Most of these tests are highly interpretive," said Cowan. "There are the results themselves, and then what they mean. I never offer the results without written clinical interpretation and recommendations for follow-up testing, when appropriate. I contact the physician directly when a true abnormality is suspected or confirmed."

Current California law requires that every newborn be screened for the following disorders:

• Phenylketonuria

• Galactosemia

• Congenital hypothyroidism

• Sickle cell anemia

This list is expected to grow sharply within the next year.

Parents of newborns at Packard Children’s Hospital are currently being offered screening for several other diseases through a statewide pilot program; positive results are confirmed in the Biochemical Genetics Laboratory.

Data from the program will help identify new diseases to include in a mandatory screening process.

"We think we can pick up in excess of 30 diseases with the technology we have now," said Cowan. "Many of these are appropriate for mandatory screening because the children are asymptomatic at first, there is an available treatment, and they can have very bad outcomes without treatment."

Some of the tests, however, identify disorders for which there is no treatment, resulting in information that is ethically tricky to handle.

Some parents don’t want a peek into a bleak future, while others value the chance to avoid long, uncertain diagnostic procedures as a child becomes ill. Further complicating the matter, some incurable diseases have a better outcome with an earlier diagnosis.

One disease that can be treated is methylmalonic academia, an inherited metabolic disorder that causes the buildup of methylmalonic acid in the body.

Symptoms, which can range from coma to lethargy and hypotonia, usually develop 24 to 48 hours after a normal delivery when the infant has his or her first protein feed. Although limiting protein in the diet can control the symptoms, it’s not always immediately obvious what is wrong with the baby.

"Often these kids are treated for a sepsis-like picture," said Cowan, "with dextrose and rehydration. They usually improve and are sent home, but if they’re not properly diagnosed they may have a recurrent episode weeks or months later."

Other metabolic disorders not included in the current newborn screen may also escape notice until an unfortunate combination of events, perhaps illness coupled with a meal bursting with protein, triggers a lethal biochemical cascade.

"Sometimes older children are not diagnosed quickly, because physicians assume they’re so old that a metabolic disorder can’t be the problem," said Cowan. "But the biochemical pathways are inter-related, and metabolic reactions can be influenced by environment or illness."

Cowan is also working closely with the hospital’s Molecular Diagnostics Laboratory to implement DNA testing to identify other genetic diseases like cystic fibrosis.

In addition, she envisions a day in the Biochemical Genetics Laboratory when enzyme activity from chorionic villi or amniotic fluid will be used to diagnose inherited disorders before birth.

Although the laboratory’s capabilities are remarkable and the plans for future testing impressive, Cowan emphasizes that the first step in a diagnosis is physician awareness of the disorders and their symptoms.

"One of the most important things to remember about these diseases is that many are treatable, but only if you know exactly what you’re dealing with," said Cowan. "They exist at every hospital, it’s just a matter of thinking to order the tests."

Packard adopts comprehensive radiology approach (3/12/03)

Pediatric surgery clinical trial is unorthodox approach to addressing disorder (1/9/00)