Ideally each infant should be tested for MSUD on the day after birth with results reported within 24 hours. The earlier these children are diagnosed and treated, the less risk of permanent damage. In the United States, all states screen newborns for MSUD through the State's newborn screening program. In countries that do not include MSUD in their screening programs, children with MSUD can become severely handicapped or die before they are diagnosed. Early diagnosis is of paramount importance if the child with MSUD is to develop normally. This should be the goal of all testing for MSUD.

Some variant types of MSUD may be missed with screening programs. Any child at risk or suspected of having MSUD should be tested. If the result is positive, or suspected to be positive, treatment should be started immediately.