An atypical case of FA2H-related HSP35 with subtle neuroimaging findings and a novel variant in a young adult with spastic paraparesis.

Abstract

We report a young Indian woman with a homozygous deletion in FA2H manifesting with a progressive spastic paraparesis, skeletal deformities, and subtle oculomotor signs, thereby broadening the phenotypic spectrum of HSP35. Except for diffuse spinal cord atrophy in MRI, other investigations were non-contributory. Whole exome sequencing with mitochondrial analysis revealed a homozygous variant c.32_34delTCT (p.Phe11del) in FA2H gene in Exon 1 of chromosome 16-a likely pathogenic, autosomal recessive mutation (ACMG: PM2,PM4,PP4-Moderate). This report underscores the importance of considering FA2H-related HSP even in late-onset or atypical presentations of adult-onset spastic paraparesis, especially in consanguineous populations, even when classical imaging findings are absent. Genetic testing remains crucial for diagnosis, prognostication, and counselling.