A novel variant in the ALDH3A2 gene causative of Sjögren–Larsson syndrome evaluated in silico aids in proper genetic counseling and planning management

Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disorder caused by mutations in the ALDH3A2 gene, resulting in a deficiency of the enzyme fatty aldehyde dehydrogenase (FALDH). This study presents the findings of a case involving an 18-month-old female child with congenital ichthyosis and feeding difficulties who was referred for genetic testing. Next-generation sequencing identified a novel homozygous variant, c.1150A>C (p. Thr384Pro), contributing to the child’s clinical presentation. In silico analyses supported the pathogenicity of this variant, indicating its detrimental impact on protein function and stability. This study highlights the critical role of FALDH in lipid metabolism and the characteristic symptoms of SLS, including skin and neurological manifestations. Management strategies focus on symptomatic relief through topical moisturizers and dietary modifications, emphasizing a multidisciplinary approach to patient care, especially in low-resource settings where gene therapy is not yet an option. The findings underscore the importance of thorough genetic counseling for affected families, guiding reproductive decisions based on the identified variants, and enhancing understanding of the disease’s complex mechanisms. This research contributes to the overarching goal of improving patient outcomes and advancing therapeutic strategies for genetic disorders like SLS.