Psychiatric Symptoms Associated with Inborn Errors of Metabolism

Inborn errors of metabolism (IEM) are individually rare but collectively common disorders, occurring in 1:800 to 1:1000 births. There are more than 1000 known inherited disorders characterized by disruption of metabolic pathways which may present with diverse symptoms affecting any organ at any age, including with psychiatric symptoms mimicking primary psychiatric disorders. This review is intended to help psychiatrists and other physicians suspect an inborn error of metabolism in a patient presenting with psychiatric symptoms. A comprehensive literature review was undertaken, using Index Medicus and resources at the University of Southern California Norris Medical Library to identify specific information for each individual disorder described. Those inborn errors of metabolism most likely to present with psychiatric symptoms primarily impact the brain, acting either directly on biochemical pathways in the central nervous system or indirectly reflecting dysfunction in other organs. Symptoms may occur episodically under stress when metabolic demands are highest or progressively evolve over time reflecting gradual neuropsychiatric deterioration. Cognitive impairment and psychosis appear to be the most frequently reported psychiatric problems. Noting age of onset, patterns of psychiatric presentation, and associated symptoms in other organ systems can increase suspicion and facilitate diagnosis of psychiatric symptoms due to an inborn error of metabolism. Psychiatric problems can be seen with multiple inborn errors of metabolism with associated systemic dysfunction or as isolated symptoms. It is important for physicians to be aware of clues that might increase suspicion of an underlying genetic disorder, and to recognize that consultation with a medical geneticist is recommended for diagnosis and to provide the patient optimal care in either situation.