Aicardi-Goutieres syndrome(s) (subclassifications 1-7); aka Familial infantile encephalopathy, with calcification of basal ganglia and chronic cerebrospinal fluid lymphocytosis

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Acronym:
AGS (includes subclassifications AGS1-7: see "Gene" area below)

SAID group:
Interferon Mediated Autoinflammatory Diseases

Gene:
Neonatal onset, high mortality: TREX1 (AGS1), RNASEH2A (AGS4), RNASEH2C (AGS3). Later onset, lower mortality: IFIH1 (AGS7), DSRAD (AGS6), SAMHD1 (AGS5), RNASEH2B (AGS2)

Inheritance:
Autosomal recessive in most cases. TREX1 and DSRAD can also present as autosomal dominant.

Ethnicity:
Not noted.

Frequency:
Unknown-rare

Timing of symptoms:
Episodes can last for months with the onset of symptoms and encephalopathy, in the first year of life. 40% have chilblains exacerbated by the cold, starting after 1 year of age. [106]. Some with continuous symptoms from birth. [104]

Age of onset:
Encephalopathy is often the first symptom noted in the first year of life, with fevers, irritability and progressive neurologic changes with flares of symptoms. 40% of patients develop chilblains lesions, starting in early childhood. 20% of cases have AGS symptoms at birth, but most are asymptomatic at birth. [104] 25% Die within the first year of age. [104], [105]

Skin cutaneous:
Chiblains are the classic skin symptom seen in 40% of patients with AGS, and may be start to develop after the first year of life. [106] They can be cold-induced and/or exacerbated by cold exposure. Chilblains can be painful, pruitic, swollen, and present on the distal areas of the ears, fingers and toes. There is a range of severity, from cold fingers and toes, and/or erythematous plaques to severe tissue damage and auto-amputation. [106] Microvascular vasculitis noted. [104], [106]. May present with purpura, petechiae, acrocyanosis. Neonatal jaundice in some patients. [105] Some have aphthous ulcers [104]

Neurologic:
Fever lasting days or weeks during attacks of symptoms, with Irritabiliity. Some have seizures. Progressive encephalopathy and cerebral atrophy, mental delay and damage, starting in infancy. [104], [105], [106] Worsening microcephaly. [105]. Worsening cognitive and mental regression with deficits, that can progress to a persistent vegetative state, or death. Dystonia, Low IQ [105]. Calcifications in the white matter, or basal ganglia noted. [105]. Leukoencephalopathy. Lymphocytosis in the CSF. [105]

Auditory:
Not noted. [104], [105], [106]

Ophthalamic:
Progressive eye involvement due to neurologic damage. [105]. Glaucoma, and/or cataracts in some cases. [106] Visual inattention. [104], [105], [106] and ocular jerking in some cases. [107]

Cardiopulmonary:
Not noted. [104], [105], [106]

Abdominal:
Vomiting, feeding difficulties are common. [107] Uncommon: hepatomegaly, splenomegaly (hepatosplenomegaly) [104], [105], [106].

Lymphatic:
Some cases with splenomegaly. [105], [106]

Joints bones muscles cartilage:
Some with stiff joints. Spasticity, dystonia of the limbs or hypotonia of the trunk noted. [104]

Vasculitis:
Vasculitis in the small vessels noted on skin biopsy of distal lesions from chilblains. [106]

Amyloidosis:
Not noted. [104], [105], [106]

Abnormal labs:
High: Liver enzymes, abnormal liver function tests (LFTs). CSF lymphocytosis, with increased serum and CSF alpha interferon levels. [104]. Low: Thrombocytopenia, Normal: ESR, CRP, ANA, lupus anticoagulant, Anticardiolipin, antiphospolipid, IgG, IgM, cryoglobulins, alpha-1 antitripsin. [106]

Search Keywords:
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