A Rare Case of PYCR2-related Hypomyelinating Leukodystrophy (HLD10) in India Presenting as a Cerebral Palsy Phenotype

Background: Hypomyelinating leukodystrophies (HLDs) are rare, progressive, autosomal recessive disorders that impair the central nervous system (CNS). The PYCR2 (Pyrroline-5-carboxylate reductase 2) gene mutations cause HLD type 10, leading to microcephaly, hypotonia, developmental delay and intellectual disability. Case Summary: We report a four-year-old boy from Karnataka, India, born to a second-degree consanguineous union, presenting with global developmental delay, progressive microcephaly, hypotonia and limb weakness, where the condition was categorised as cerebral palsy (CP). Whole-exome sequencing (WES) identified a homozygous PYCR2 variant (NM₀13328: c. 751C>T; p. Arg251Cys), confirmed by Sanger sequencing, with heterozygosity in both parents and the elder sibling. This study represents the third reported case in India. Conclusion: This study highlights the importance of a molecular diagnostic approach for CP mimics. Identification of mutations enables accurate diagnosis, informed genetic counselling and early interventions, as well as recurrence prevention, emphasising the need for awareness of rare HLDs in clinical practice.