Genome sequencing aiding diagnosis of birth disorders, treatment in hours

KARACHI: Genome sequencing of a 5-week-old child at the Rady Children’s Hospital in San Diego, USA within a few hours of admission at the health facility led to clinical diagnosis of a congenital metabolic disorder and start of a treatment that saved the infant’s life, a report in The New England Journal of Medicine said.

According to the report in the NEJM, the 5-week-old, previously healthy male infant was admitted after 2 hours of inconsolable, atypical crying and irritability and radiological examinations revealed that the child was having early infantile encephalopathy.

As parents of the child had already lost a child with similar neurological conditions ten years earlier, doctors and experts at the Rady Children’s Hospital decided to seek a diagnosis through genome sequencing. “We obtained blood samples 17 hours after admission and performed genome sequencing”, and its results led to diagnosis of thiamine metabolism dysfunction syndrome 2 (THMD2) within 14 hours 33 minutes after his blood samples arrived at the genome center, doctors and experts said. They said this provisional diagnosis was clinically confirmed 49 minutes later while video electroencephalography showed numerous seizures occurring in the interim.

“Thiamine and biotin (vitamins of B complex) administration was started 37.5 hours after admission, and phenobarbital administration was started 2 hours later.Six hours later, the patient was alert, calm, and taking bottle feeding,” the report in the NEJM said, adding that after a further 24 hours passed without seizures, the patient was discharged. He is now thriving at 7 months of age.

According to the experts infantile encephalopathy is associated with approximately 1500 genetic diseases, many of which are clinically indistinguishable but have unique, effective treatments. Without prompt treatment, permanent neurologic injury or death occurs in many infants with these diseases.

The article further says prompt treatment based upon genome sequencing illustrated the fulfillment of the promise of the Human Genome Project to transform healthcare. This illustrates the potential for decreased suffering and improved outcomes through the implementation of rapid genome sequencing in a multidisciplinary, integrated, precision medicine delivery system, the article said.

“The system includes identification of infants with suspected genetic diseases on the day of admission, rapid genome sequencing as a first-tier test, communication of results facilitating prompt transition from empirical to etiologically informed treatment, and implementation within a learning health care system,” it further said. Currently, rapid genome sequencing is being implemented in Australia, England, Germany, and Wales and in Medicaid pilot programs in California, Florida, and Michigan, the NEJM article said.