Monogenic SAMHD1 Aicardi-Goutières Syndrome Type 5; Challenges in Diagnosis and Management: A Case Report

Author(s): Hamdan Iftikhar Siddiqui, Ali Omar Abdulatef Al Yasari, Muneeb Mazhar, Habibullah Abdullah, Saif Abdullah, Subhranshu Sekhar Kar, Rajani Dube

Background: Aicardi-Goutières syndrome is a rare autosomal recessive neurogenetic disorder characterized by progressive neurodegeneration, basal ganglia calcifications, leukodystrophy, and chronic cerebrospinal fluid lymphocytosis. Due to the rarity of the condition, there is a lack of specific guidelines for optimal management of these patients. Through this case, we are reporting a mutation in the SAMHD1 gene in the form of homozygous deletion, which is a rare etiology of AGS.

Case Presentation: This report describes an 18-month-old male child with a complex clinical presentation, including microcephaly, developmental delay, quadriplegia, hypotonia, and spasticity. The patient, born to consanguineous parents, was admitted with fever and showed typical neurological features, such as decorticate posturing, a positive Babinski sign, and spastic quadriplegia. Laboratory findings revealed elevated liver enzymes and abnormal lymphocyte distribution. Genetic testing via whole exome sequencing identified a homozygous deletion in exon 2 of the SAMHD1 gene, leading to a pathogenic variant. This mutation is associated with AGS5, contributing to the understanding of AGS genetic variability and emphasizing the importance of early genetic testing for accurate diagnosis. The clinical features align with AGS, supporting the novel detection of SAMHD1 mutations in this context.

Conclusion: This case highlights the critical role of whole genome sequencing in early diagnosis, genetic counseling, and management of AGS. It will contribute to the broader knowledge of the disease spectrum, encouraging further research into AGS.