Aicardi-Goutières Syndrome: Brief Case Report.

The case of a term newborn diagnosed with Aicardi-Goutières syndrome, a rare encephalopathy in our environment, with Mendelian inheritance pattern, characterized by a set of nonspecific neurological symptoms associated with typical findings of intracerebral calcifications. The case is presented with diagnostic imaging, in addition to elevated levels of interferon alpha and cerebrospinal fluid lymphocytosis.

INTRODUCTION

Aicardi–Goutières syndrome (AGS) is a rare hereditary encephalopathy, characteristic of the first year of age. It is characterized by several phenotypes, mainly dystonia and spasticity, associated with radiological evidence of intracranial calcifications, abnormalities of white matter and cerebral atrophy, in addition to lymphocytosis and high levels of interferon alpha (IFN-α) in cerebrospinal fluid (CSF).[12]

Then, we present a case of a patient with SAG diagnosed in our service, and a brief review of the subject is made based on the bibliographic search, with special emphasis on the radiological aspect.

CASE REPORT

A newborn male of 3,500 g, the product of a first supervised pregnancy, and finalized by vaginal delivery at 38 weeks of gestation, which required invasive ventilation and therefore entry to a neonatal intensive care unit. During the stay, he presented an only convulsive episode of generalized clonic type, attributed initially to possible cerebral hypoxic phenomenon, which responded well to the administration of phenobarbital.

Pathological findings at the cephalocaudal physical examination were increase of cephalic perimeter with union of anterior and posterior fontanels, horizontal nystagmus, miotic pupils, reticulated skin with acrocyanosis and hypotonia. After extubation, they impressed the poor suction and hypoactivity. Electroencephalography showed beta diffuse rhythm (sleep), transfontanellar ultrasonography revealed hydrocephalus and diffuse cerebral atrophy, and serum ammonium value was 75.5 μmol/L. Once the diagnosis was made, adequate medical management was performed with carglumic acid, 90 mg every 6h, phenobarbital, and neurosensory stimulation therapies. Brain CT and MRI were performed with the usual findings of Aicardi-Goutières Syndrome (CT-involvement of the periventricular white matter)/(IRM T1 weighted image hypointensity of white matter as a sign of leukodystrophy) [Figures 1 and 2A, B]. The patient has continued ambulatory monitoring with pediatric neurology.

Figure 1

Cranial tomography, involvement of the periventricular white matter

Figure 2

(A and B) Magnetic resonance 1) T1 weighted image hypointensity of white matter as a sign of leukodystrophy

DISCUSSION

In 1984, Jean Aicardi and Francoise Goutières reported eight patients from five families who had a type of familial-onset encephalopathy with chronic lymphocytosis in CSF and calcifications of the basal ganglia but with negative TORCH (toxoplasmosis, rubella cytomegalovirus, herpes simplex, and HIV) studies. It may appear immediately after delivery or after a period of apparent normal development, and it may include other neurological manifestations such as hypersensitivity to sound stimuli, irritability, poor head support, hypotonia, seizures, progressive microcephaly, and/or psychomotor retardation, in addition to extraneurological manifestations, where the skin is the most affected organ—perineum erythema, periungual erythema, etc. Intermittent fever is an almost constant sign in all patients.[34]

It has an autosomal-recessive Mendelian inheritance pattern (No. *225750) and its origin is derived from the mutations that undergo the different genes encoding the RNases, in charge of degrading intracellular RNA chains.[5] The excess of the latter induces the production of Toll-like receptors dependent on IFN-α, and this, in turn, triggers a neurotoxic lymphocytic response and inhibits cerebral angiogenesis, giving rise to the radiological alterations already described. In 2009, Crow and Livingston[6] identified the five specific loci determining mutations in the SAG, thus explaining the heterogeneity of the clinical cases presented in the different series. Thus, mutation 1 occurs on chromosome 3p21; 2 on 13q14.3; 3 on 11q13.2; 4 on 19p13.13; and 5 on 20q11. All contributors to the genesis of approximately 90% of the cases have been described.[78]

SAG should always be considered in neonates with symptoms suggestive of congenital infections but with negative exams. Cordocentesis and measurement of fetal serum levels of IFN-α may be of great utility with ultrasound and findings suggestive of SAG and a positive family history.[6910]

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Conflicts of interest

There are no conflicts of interest.