Complicated Spastic Paraparesis: Study of a Patient With a De Novo Pathogenic Variant in <i>ELOVL1</i>

Very long-chain fatty acid elongase-1 (ELOVL1) is essential for fatty acid elongation and is widely expressed in numerous tissues, including the central nervous system, being involved in the elongation of very long-chain fatty acids (VLCFAs), which are essential for biological processes such as myelin formation. Monoallelic pathogenic variants in ELOVL1 have been described in association to a condition characterized by ichthyosis, spasticity, nystagmus and cerebral hypomyelination, although a similar but more severe presentation has been reported in patients with biallelic variants. We report the case of a new patient affected by ELOVL1-related leukodystrophy. Clinical data regarding pregnancy, delivery, age and symptoms at onset, psychomotor development and molecular diagnosis were systematically collected, as well as data on disease complications, neurological progression, the possible occurrence of epileptic seizures and instrumental examinations performed. The clinical picture was characterized by congenital ichthyosis, progressive spastic paraparesis and nystagmus. Brain MRI showed slightly progressive supratentorial and infratentorial white matter abnormalities, associated with thinning of the corpus callosum. Genetic analysis identified the de novo pathogenic variant p.Ser165Phe in ELOVL1. Although the spectrum of VLCFA catabolism defects is well documented, little is still known about disorders related to their biosynthesis. This study highlights the need to consider ELOVL1 mutations in the differential diagnosis of a child presenting with white matter abnormalities, progressive spastic paraplegia and congenital ichthyosis and emphasizes the importance of thorough neuroradiological and genetic investigations in the diagnosis and understanding of this rare neurometabolic disorder.