POLR3-Related Leukodystrophy: A Case Series from the Indian Scenario

POLR3-related leukodystrophy is a spectrum of hypomyelinating leukodystrophy caused by biallelic POLR3A, POLR3B, POLR1C, and POLR3K variants. This series of case reports aims to provide a concise overview of the spectrum of rare hypomyelinating leukodystrophy caused by POLR3 variants and adds to the existing knowledge regarding clinical details of a rarer subset caused by POLR1C variant. A retrospective review of four cases in the POLR3-related leukodystrophy spectrum was done. Data pertaining to the clinical details, radiological features, and genetic results of the patients were retrieved and analyzed. Hypomyelination, hypodontia, and hypogonadotrophic hypogonadism are the core features of this spectrum of disorders, and our children from North India also had similar presentation. Sensorineural hearing loss is a newly reported feature, seen in our patients. Further research and larger studies are needed on the pathogenetic cellular mechanisms in this form of hypomyelinating leukodystrophy to guide development of therapeutic targets.