New Delhi, Oct. 3: A test that combines whole genome sequencing with software programs allows doctors to screen acutely ill newborn babies for hundreds of genetic disorders within 50 hours of birth, scientists announced today.
They said their testing method cuts the diagnosis time from the current four to six weeks to only two days, allowing doctors and parents to take critical and timely decisions about treatment options for babies born with serious genetic disorders.
Researchers at the Children’s Mercy Hospital (CMH) in Kansas City in the US who developed the test said it might, in some cases, help doctors start therapy to prevent disabilities or life-threatening illness in newborns with genetic disorders.
In other cases where the genetic disorders have dire outcomes, the researchers said, doctors could counsel parents and, if requested, stop unnecessary treatment of their newborn in intensive care units.
Stephen Kingsmore, director of pediatric genomic medicine at the CMH, told The Telegraph via email that researchers at the CMH are working with pediatric genetics experts at the Sir Ganga Ram Hospital, New Delhi, to provide similar testing for children in India.
“This is going to transform neonatology by allowing (doctors) to practise medicine influenced by genomes. Until now, they’ve really had to practise medicine blindfolded,” he told reporters yesterday.
The CMH and collaborating institutions have described their work today in the journal Science Translational Medicine.
Researchers have over the past two decades catalogued 3,528 single gene disorders present during the first 28 days of life, among which at least 70 disorders may be treated to prevent disabilities or deterioration of health.
For example, a disorder of abnormal glycogen accumulation in the body may be treated with enzymes. A fatal genetic disorder of the nervous system called Krabbe disease may be treated with cord blood transplants before the start of symptoms, which happens between three and six months of age. And a condition called phenylketonuria may be prevented from causing disease through diet control.
“This is an important advance relevant to India where we see consanguineous (among relatives) marriages and marriages within communities,” said Ratna D. Puri, a pediatric geneticist at the SGRH, who was not connected with the research but is collaborating with CMH for testing.
Such marriages carry the risk of disease-linked genes being passed to the offspring.
“Identifying the genetic disorder is the first step to helping the family — it can help the parents take informed decisions about prognosis, treatment options or pave the way for counselling,” Puri said.
Doctors caution that the test is still expensive — $13,500 (Rs 7 lakh) in the US — and is not ready yet for routine hospital use. Kingsmore himself said that studies to show the test’s cost-effectiveness are yet to be done.
The test combines whole genome sequencing with two software programs into a new diagnostic tool that limits genome analysis and interpretation to what is relevant to a baby’s symptoms as reported by neonatologist.
The tool named symptom and sign-assisted genome analysis (SSAGA) now looks at 595 genes, but the researchers plan to expand this to all the 3,500 known disease genes, Neil Miller, a team member and head of informatics at the CMH, told the teleconference.
Doctors say even when the prognosis is dire, the test will have uses.
Kingsmore said in cases where there is no treatment, parents may take decisions on moving the baby from intensive care units to regular beds “where there can be some bonding and where the family can grieve and say goodbyes.”
He said the test is designed to be used in acutely ill babies who are believed to have a genetic disorder. “The test would not make sense in healthy babies, nor would it have a cost-benefit ratio that was acceptable in these babies, even though it may pick up illnesses even before they had caused symptoms,” Kingsmore said.
Doctors believe the number of genetic disorders for which treatments are available may also grow in the future. “Even if the proportion of treatable diseases today is small, such research is important to pursue,” said Sanjay Pai, a pathologist in Bangalore and member of the Forum for Medical Ethics, who was not connected with the research.
The CMH team used a sequencing machine in Essex, England, which meant delays due to shipping samples. The test results were thus available only after six days. But if the equipment is on the same premises, the test sequence would take 50 hours.
Several hospitals across India have for over a decade been offering prenatal diagnostic tests for certain single gene disorders such as hemophilia, beta-thalassemia, Fragile-X syndrome, muscular dystrophy, and cystic fibrosis, among others.
Puri said genome science has not advanced to a point yet where such a whole genome sequencing technique could be offered as a prenatal diagnosis. “In the prenatal stage, we cannot be sure that gene variations will be associated with disease,” she said.
The CMH team used the test — which relies on a single drop of blood — on four babies and, doctors say, the results of the tests and the outcome of the babies is a poignant reminder of the advances and limitations of medical science.
The researchers identified a fatal neonatal epilepsy in a girl, a blistering skin condition in a boy, but failed to identify the cause of illness in another boy. All three babies died. In the fourth child, the scientists detected what they suspect is a novel gene mutation for congenital abnormalities of the heart and other organs. When the scientists sent their paper for publication, the baby was awaiting cardiac surgery.