Development of Neuropsychological Functions in Patients with Glutaric Aciduria Type I

Background: Glutaric aciduria type I (GA-I) is an autosomal recessive inherited metabolic disease due to a deficiency of glutaryl-CoA dehydrogenase, which if untreated results in severe neurological impairment. Combined metabolic treatment (low-lysine diet, carnitine supplementation, and emergency treatment) according to evidence-based guideline recommendations (Kölker et al 2011) has significantly reduced the manifestation of striatal injury and secondary dystonia in glutaric acidemia type I (GA-I) patients. However, development of cognitive functions in these patients has not yet been studied in detail.

Methods: In a cross-sectional design, 31 patients detected by newborn screening (n = 13), high-risk family screening (n = 3), or selective screening (n = 14) were tested for the following: (1) Simple reaction time (SRT), (2) continuous performance (CP), (3) visual working memory (VWM), (4) tracking (T), and (5) visual search (three loads: VS1, VS2, and VS3). Dystonia, observed in 13 patients (42%), was categorized for severity using the Barry-Albright Dystonia Scale (BADS). Patients’ data were compared with a cross-sectional control group of 196 healthy subjects covering the same age range. Developmental functions of cognitive performance were analyzed using a negative exponential function model.

Results: Compared with asymptomatic patients dystonic patients showed poorer performances in speed motor tests (SRT and tracking). Tests with higher cognitive load (CP, VWM, and VS) were not associated with BADS score. Development of cognitive performance in GA-I patients did not differ from healthy control for mean CP, tracking, and VWM but in contrast was different for SRT and VS3; data fitted equally well to a negative exponential function. However, patients in younger age groups performed consistently poorer but consistently caught up with age.

Conclusion: In summary, our results show that dystonia in GA-I patients results predominantly in motor speed impairment, but not in information processing like memory. Furthermore, stability of speed is comparable to healthy subjects, in particular showing no decline over time. Results indicate normal developmental functions in GA-I patients, however, with increased reaction times.