~30 years after the start of the Human Genome Project, we sequenced the genome of an infant with encephalopathy in just over 11 hours. The results led to a clinical diagnosis of thiamine metabolism dysfunction syndrome 2 (THMD2) 16.5 hours after a blood sample was obtained and 13 hours after we initiated sequencing, which informed treatment of the infant, thereby illustrating the fulfillment of the promise of the Human Genome Project to transform health care…Video electroencephalography showed numerous seizures occurring in the interim. Thiamine and biotin administration was started 37.5 hours after admission, and phenobarbital administration was started 2 hours later. One 15-second seizure was recorded thereafter. 6 hours later, the patient was alert, calm, and bottle feeding. Standard, trio genome sequencing confirmed the diagnosis. After a further 24 hours passed without seizures, the patient was discharged. He is now thriving at 7 months of age.
…Ten years earlier, his parents, who were first cousins, had had a child with a similar neurologic presentation that rapidly progressed to epileptic encephalopathy; the child died at 11 months of age without an etiologic diagnosis, despite extensive evaluation.
…This case illustrates the potential for decreased suffering and improved outcomes through the implementation of rapid genome sequencing in a multidisciplinary, integrated, precision medicine delivery system…Currently, rapid genome sequencing is being implemented in Australia, England, Germany, and Wales and in Medicaid pilot programs in California, Florida, and Michigan.
