Inborn errors of metabolism (IEM) are comprised of single gene defects that result in a decrease in function or absence of a specific enzyme leading to an accumulation of toxic compounds. This chapter presents assessment, diagnosis, and treatments for children with a diagnosis of IEM as well as insights into the comorbid behavioral health problems that may occur in these children. Pediatric primary care providers (P-PCPs) are the leaders in the medical home for children with a diagnosis of IEM. This chapter describes numerous IEM and the various behavioral and mental health problems that are related to the individual IEM such as phenylketonuria, galactosemia, congenital adrenal hyperplasia, X-linked adrenoleukodystrophy, Wilson disease, urea cycle disorders, cobalamin C disorder, Gaucher disease, Fabry disease, and porphyria. P-PCPs have the opportunity to intercept outcomes through early identification of signs and symptoms of behavioral problems, assessment and screening of the child, and referral for treatment.