All states in the United States screen for MSUD through newborn screening programs. Newborns should be tested 1-3 days after birth with results reported within 24 hours. Early diagnosis and treatment within the first 10 days of life reduces the risk of permanent damage and allows for normal development. In countries that do not screen for MSUD in the neonatal period, children with MSUD may become severely handicapped or die before they are diagnosed.

Variant MSUD may be missed during newborn screening. Any child at risk or suspected of having MSUD should be tested promptly with a plasma amino acid panel and treated immediately if the results are positive or suspect.