Aicardi-Goutieres Syndrome 3 is a rare disorder with severe neurological and immune system manifestations.  Affected individuals suffer from encephalopathy which results in brain deformities such as delayed myelination, white matter abnormalities, a thin corpus callosum and intracranial calcifications. Patients exhibit extreme irritability, intermittent fevers (sterile pyrexias), progressive microcephaly, hypotonia, dystonia, and psychomotor regression. Immune system anomalies include increased alpha-interferon levels in the serum and CSF as well as CSF lymphocytosis.  Chilblains are another hallmark of AGS3.  These are puffy, red, itchy and painful lesions that occur on the fingers, toes or ears and are caused by the inflammation of small blood vessels.  AGS3 is a progressive disorder with an onset in early infancy.  About 80% of the patients presenting with severe forms of AGS die within the first decade of life.  So far, AGS does not appear to have a gender or racial bias.

Diagnosis can be made based on MRI scans that help identify brain anomalies and by spinal taps which allow cerebrospinal fluid to be analyzed for lymphocytosis and an increase in interferon alpha activity.  While there is currently no cure for the disorder, supportive and symptomatic treatments such as physical therapy may help patients based on their individual needs. 

AGS3 follows an autosomal recessive pattern of inheritance and is caused by homozygous mutations in the RNASEH2C gene.  This gene encodes a subunit of the RNase H2 ribonuclease enzyme complex involved in the degradation of RNA from DNA:RNA hybrids.  Mutations in this gene generally result in a dysfunctional RNase H2 complex and the resulting accumulation of excess DNA and RNA in the cells elicits an immune response by the body.  So far, the missense mutations p.R69W and p.K143I have been linked to the disorder.