P56 Challenges in rare diseases diagnostic: aicardi-goutieres syndrome – a case report

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Background and Aim

In Europe, rare diseases are considered the pathologies that affect fewer than 1 in 2000 persons. More than 6000 rare diseases were identified, and almost 80% of them have a genetic cause. Many rare disorders are characterised by a broad diversity of common symptoms and signs leading to misdiagnosis and delaying treatment. Aicardi syndrome is a rare disorder mainly characterised trough agenesis or dysgenesis of the corpus callosum, seizures and chorioretinal lacunae, affecting about 1 in 1 05 000 to 1 67 000 newborns. It is estimated that there are approximately 4000 affected individuals worldwide. This case report aims to outline the difficulties met in the diagnostic process of a case with Aicardi-Goutieres syndrome and the importance of a multidisciplinary medical team in rare diseases diagnostic.


We have investigated an 18 months old girl with hemiparesis and generalised hypertonia starting at the age of 9–10 months. MRI showed leukoencephalopaty, mostly suggestive for a lysosomal storage disorder. The metabolic work-up including serum ammonia and lactate, tandem mass and urine organic aminoacid was inconclusive. The lysosomal disease panel performed was negative.


DNA isolated and purified from peripheral venous blood was further assessed by NGS platform (Mi-Seq, Illumina) using a panel containing 26 genes responsible for leukodystrophies.


Assessment through NGS panel identified two different mutations in RNASEH2B gene: c.529G>A (p.Ala177Thr) and c.554T>G (p.Val185GLy). The result was further validated through Sanger sequencing. Sanger sequencing of both parents revealed that the mother was carrier for c.554T>G (p.Val185GLy) mutation, while the father carried the other mutation identified in the child.


Based on literature review (scientific papers and international databases like DECIPHER and OMIM) we were able to correlate the clinical phenotype identified our patient with the mutations obtained through NGS assessment. The clinical diagnostic of this patients was Aicardi – Goutieres syndrome.


Genetic results may offer significant data to make possible phenotype- genotype correlation. Therefore, genetic testing plays an important role in the diagnosis and future management of rare disorders


Key-words: rare diseases, Aicardi syndrome, RNASEH2B mutation

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