Fig. 2: Brain imaging and ophthalmological findings in PAICS-deficient patients.

A–C Brain image changes in patient 1 axial MRI at 3 months of age. Axial T1-weighted MRI image A revealed visible myelination of only the posterior limb of the internal capsules (arrowheads), enlargement of the ventricles, chronic subdural effusion predominantly in the frontotemporal region, and widened Sylvian fissures with failed operculization. These features were also evident in axial T2-weighted imaging B, C. D–J Axial MRI and MRS in patient 1 at 7 months of age. Axial T2-weighted imaging revealed more extensive cerebral atrophy and hyperintensities observed in both frontal, temporal areas and the putamen (arrowheads) D, E. Diffusion-weighted imaging (DWI) demonstrated restricted diffusion coefficients at both globus pallidum F, both cerebral peduncles G, and the central pons H. Magnetic resonance spectroscopy (MRS) of metabolites at long TE showed reduced NAA/Cre and NAA/Cho ratios, elevated Cho/Cre ratio, and the presence of lactate duplets (arrowheads) I, J. K, L Axial MRI in patient 1 at 13 months of age. Axial T2-weighted imaging of revealed rapid atrophy of cerebrum accompanied by notable subdural effusion. M, N Brain image in patient 2 at the age of 1 year. Axial T2-weighted imaging revealed poor myelination of the anterior limb of the internal capsules (arrowheads), enlargement of the ventricles, cerebral atrophy with frontotemporal predominance, and widened Sylvian fissures with failed operculization. O–R Fundus photos of patient 2 at the age of one year and patient 1 at the age of 7 years. The pictures showed significant retinal pigmentary changes and atrophy in the macular area in bilateral eyes, suggesting the presence of macular dystrophy O, P in patient 2. Similar but more pronounced and extensive features of the fundus were also observed in patient 1 at the age of 7 and a half years, implying a deteriorating disease course Q, R.