Novel SLC13A3 Variants and Cases of Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation and Literature Review

Objectives Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is a recently described autosomal recessive leukoencephalopathy caused by pathogenic variants in the SLC13A3 gene. ARLIAK is characterized by acute neurologic involvement, often precipitated by febrile illness, with largely reversible clinical symptoms and imaging findings. Three patients have been reported in the literature to date. Our objective is to report newly identified patients and their genetic variants and phenotypes and review published literature on ARLIAK. Methods This report contributes 4 additional patients to the literature; describes novel variants in SLC13A3; and reviews genetic, biochemical, clinical, and radiologic features of all published patients with ARLIAK. Results We provide additional genetic, imaging, and laboratory insights into ARLIAK, an atypical leukodystrophy with clinical and radiologic findings that can normalize. Discussion Our case series highlights the importance of reanalysis of next-generation sequencing in the diagnostic workup.