A clinical case of POL3A-associated hypomyelinating leukodystrophy with spinal cord lesion with a debut in early childhood

Abstract

Leukodystrophies are a group of hereditary progressive diseases of the central nervous system characterized by selective lesions in white matter with specific involvement of glial cells. There are hypomyelinating (absence of myelin deposition), demyelinating (loss of previously deposited myelin), dysmyelinating (deposition of structurally or biochemically abnormal myelin), and myelinolytic leukodystrophies (myelin vacuolization). Hypomyelinating leukodystrophies (HL), like most leukodystrophies, debut in childhood or adolescence and are characterized by a progressive course of the disease. HL occurs as a result of impaired synthesis of proteins responsible for the development, structure, and integrity of the myelin sheath, involved in the processes of transcription and translation. In the latter group, the main role is assigned to HL associated with biallelic mutations in the genes of the RNA polymerase III transcription complex, POLR3: POLR3A, POLR3B, POLR1C, and POLR3K. The diagnosis can be confirmed by magnetic resonance imaging of the brain. POLR3A-associated HL is manifested by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. The magnetic resonance features of POLR3-associated HL include diffuse hypomyelination with relative preservation of the dentate nuclei, anterolateral nuclei of the thalamus, globus pallidus, pyramidal tracts at the level of the posterior part of the internal capsules, and the corona radiata. In some cases, thinning of the corpus callosum and atrophy of the cerebellum were also noted. The article presents a clinical case of a patient with POL3A-associated HL with spinal cord injury with the debut in early childhood.