Objective:

To review the clinical features of adult-onset inborn errors of metabolism (IEMs) presenting with neuropsychiatric symptoms.

Background:

Awareness of IEMs presenting in adulthood is increasing. The potentially treatable nature of some of these conditions warrants consideration during the evaluation of patients. However, the rarity and plentitude of individual IEMs make their inclusion in clinical practice cumbersome.

Design/Methods:

We conducted a retrospective systematic review of the literature on treatable adult-onset IEMs up to September 2022. We obtained the clinical features of each case, including presentation course,  neuropsychiatric and neurological symptoms.

Results:

We identified 192 cases in 14 IEMs. We divided the IEMs into four categories based on their pathophysiology: 1) energy deficits 2) intoxications 3) metal storage disorders, and 4) lysosomal storage disorders. Energy deficits presented with an acute (53.1% of cases) or episodic (34.4%) course. Impaired arousal (18.7%) and seizures (37.5%) were the most common neurological symptoms. Intoxications had an acute onset in 44.1% of cases. The most common neuropsychiatric symptom was psychosis (26.5%) and acute polyneuropathy was present in 20.6% of cases. Metal storage disorders had a chronic time course (76.3%) with memory impairment (26.5%) as the most common neuropsychiatric symptom. Lysosomal storage disorders progressed over a chronic time course (84.1%). Multidomain cognitive presentations were seen in 43.2% of patients,  memory and language dysfunctions were the most common deficits. Spasticity and weakness were noted in  28.4% of cases. 

Conclusions:

Neuropsychiatric symptoms are common in IEM. Our retrospective showed that the time course, neuropsychiatric symptoms at onset, and associated systemic symptoms are informative in establishing the IEM subtype underlying a neuropsychiatric presentation.