Aicardi-Goutières Syndrome (AGS) is a leukodystrophy characterized by early neurologic disability. Although AGS is genetically heterogeneous, all genotypes activate a common pathway: interferon (IFN) production leading to Janus kinase (JAK) activation and transcription of IFN-stimulated genes. The neurologic impairment associated with AGS ranges from mild, stable spastic paraparesis (a mimic of cerebral palsy) to severe early onset disease (a mimic of congenital TORCH infections). Often there are subtle cues to aid in the recognition of AGS. We will discuss clinical monitoring guidelines for the AGS population to address the potential for systemic complications. While there is no approved treatment, there is great interest in targeting common steps along this autoinflammatory pathway. We will address the evidence surrounding therapeutic interventions from steroids and IVIG to reappropriation of targeted therapies such as reverse transcriptase inhibitors and janus kinase inhibition.
We will discuss the common laboratory abnormalities observed during the clinical trials of baricitinib. Ultimately, this complicated disorder of autoinflammation necessitates a comprehensive plan for clinical monitoring with additional monitoring while on immunomodulatory treatments.
- AGS is one of the most common leukodystrophies. We will review the early signs and symptoms of AGS to help with earlier diagnosis.
- AGS is a complicated, systemic autoinflammatory disorder. We will review a strategy for comprehensive clinical management and monitoring in AGS.
- AGS is a genetic disorder of interferon overproduction. We will review the evidence behind emerging treatment strategies such as janus kinase inhibition.