Hyperhomocysteinemia due to MTHFR deficiency - A treatable metabolic causes of progressive spastic paraparesis not to be missed

Abstract Methylenetetrahydrofolate reductase ( MTHFR ) deficiency is a rare autosomal-recessive disorder of folate metabolism, presenting with neurological symptoms such as spastic paraparesis, cognitive impairment, and psychosis. We report a 25-year-old male who developed progressive spastic paraparesis over nine months, requiring assistance to walk. Neurological examination revealed increased tone, brisk reflexes, and sensory deficits. Brain MRI showed cerebral atrophy with white matter hyperintensities, and fasting homocysteine levels were elevated (143.01 µmol/L). Whole exome sequencing identified a homozygous mutation in the MTHFR gene, confirming the diagnosis of hyperhomocysteinemia. The patient was treated with high-dose vitamin B12, folate, and pyridoxine supplementation, resulting in mild improvement in spasticity and walking after one month. This case highlights the importance of considering MTHFR deficiency in young adults with unexplained spastic paraparesis and cognitive or psychiatric symptoms. Elevated homocysteine levels and genetic testing are crucial for diagnosis, and early treatment can improve clinical outcomes.