Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I
J. Clin. Invest. William J. Zinnanti, et al. 117:3258 doi:10.1172/JCI31617 [Go to this article.]

Figure 4
Brain lysine accumulation, ketotic hypoglycemia, and increased glutaric acid levels correlate with age-dependent susceptibility to brain injury in weanling Gcdh^–/– mice. (A) Serum lysine, brain lysine, and brain glutaric acid levels, (B) serum and brain arginine and alanine levels, and (C) serum glucose (Glc) and β-hydroxybutyrate levels in weanling (4w) and adult (8w) Gcdh^–/– mice (G^–/–) and heterozygous controls (G^–/+) on normal (ND) or lysine (Lys) diets. Amino acid differences are compared with heterozygous normal diet controls, and brain glutaric acid differences are compared with weanling Gcdh^–/– normal diet controls. Mean ± SEM, *P < 0.01; **P < 0.001. n = 6 each group. (D) Twelve-day survival of adult (black circles, n = 20) and weanling (black diamonds, n = 20) Gcdh^–/– mice on the lysine diet. (E) T₂ maps (top) and T₂-weighted images (bottom) of weanling Gcdh^–/– mice. Color bar indicates T₂ values (right side). Weanlings showed brain swelling, indicated by obliterated ventricles (black arrows; compare left with middle and right), and increased subdural fluid collection (red arrows, middle) at 48 hours of lysine diet exposure. At 6 days, surviving weanlings developed striatal lesions indicated by increased T₂ signal (red arrows, right).