¹H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency

Objective: To evaluate brain metabolism in subjects with partial ornithine transcarbamylase deficiency (OTCD) utilizing ¹H MRS. Methods: Single-voxel ¹H MRS was performed on 25 medically-stable adults with partial OTCD, and 22 similarly aged controls. Metabolite concentrations from frontal and parietal white matter (FWM, PWM), frontal gray matter (FGM), posterior cingulate gray matter (PCGM), and thalamus (tha) were compared with controls and IQ, plasma ammonia, glutamine, and disease severity. Results: Cases ranged from 19 to 59 years; average 34 years; controls ranged from 18 to 59 years; average 33 years. IQ scores were lower in cases (full scale 111 vs. 126; performance IQ 106 vs. 117). Decreased myoinositol (mI) in FWM (p = 0.005), PWM (p < 0.001), PCGM (p = 0.003), and tha (p = 0.004), identified subjects with OTCD, including asymptomatic heterozygotes. Glutamine (gln) was increased in FWM (p < 0.001), PWM (p < 0.001), FGM (p = 0.002), and PCGM (p = 0.001). Disease severity was inversely correlated with [mI] in PWM (r = -0.403; p = 0.046) and directly correlated with [gln] in PCGM (r = 0.548; p = 0.005). N-Acetylaspartate (NAA) was elevated in PWM (p = 0.002); choline was decreased in FWM (p = 0.001) and tha (p = 0.002). There was an inverse relationship between [mI] and [gln] in cases only. Total buffering capacity (measured by [mI/mI + gln] ratio, a measure of total osmolar capacity) was inversely correlated with disease severity in FWM (r = -0.479; p = 0.018), PWM (r = -0.458; p = 0.021), PCGM (r = -0.567; p = 0.003), and tha (r = -0.345; p = 0.037). Conclusion: Brain metabolism is impaired in partial OTCD. Depletion of mI and total buffering capacity are inversely correlated with disease severity, and serve as biomarkers.