A Case of Adult-Onset Spastic Paraparesis: A Treatable Presentation of MTHFR Deficiency

Abstract

Introduction
Spastic paraparesis in young adults often raises suspicion for neurodegenerative, demyelinating, or structural spinal cord disorders. However, metabolic causes such as methylenetetrahydrofolate reductase (MTHFR) deficiency are frequently overlooked despite being potentially treatable.
This case presents a 21-year-old male with progressive spastic paraparesis due to late-onset MTHFR deficiency and hyperhomocysteinemia, emphasizing the importance of early metabolic screening in unexplained motor syndromes. It contributes to literature by reinforcing that early intervention can halt or reverse neurological deterioration in a rare but manageable condition.
Patient Concerns and Key Clinical Findings
Demographics:
21-year-old male from Tripuranthakam
Well-built, tall; noted to have gynecomastia
Chief Complaints:
Progressive stiffness in both lower limbs for 1 year
Weakness in both lower limbs for 5 months
History of Present Illness:
Onset in left leg, followed by right
Difficulty in:
Walking without support
Climbing stairs
Rising from squatting position
Wearing footwear due to dragging of feet
Pseudobulbar affect reported (sudden inappropriate laughter/crying)
Recent swelling, pain, and discoloration in left leg
Examination Findings:
Neurological:
Conscious, oriented, MMSE: 30/30
No cranial nerve or sensory deficits
Spastic gait with grade 3 spasticity bilaterally
Bilateral extensor plantar responses
Exaggerated deep tendon reflexes (DTRs)
General:
Left leg: Tender and warm
Gynecomastia noted

Diagnosis, Interventions, and Outcomes
Final Diagnosis:
Late-adolescent onset MTHFR deficiency
Spastic paraparesis associated with hyperhomocysteinemia
Diagnostic Clues:
Progressive bilateral spasticity without sensory loss
Pseudobulbar affect
Elevated serum homocysteine levels
Confirmed MTHFR mutation (via genetic testing, if done)
Treatment Initiated:
Betaine – to support alternative remethylation of homocysteine
Pyridoxine (Vitamin B6) – cofactor for homocysteine metabolism
Folate and Vitamin B12 supplementation (if applicable)
Supportive care – physiotherapy for spasticity management

Outcome:
At follow-up, the patient showed improvement in lower limb strength, reduction in spasticity, and improved gait stability with continued betaine and vitamin therapy.
Conclusion and Key Takeaways
MTHFR deficiency, though rare, is a treatable cause of adult-onset spastic paraparesis.
Early detection and management can prevent irreversible neurological damage.
Routine homocysteine screening in cases of unexplained spasticity can aid in timely diagnosis.
This case underscores the importance of metabolic workups in young patients with upper motor neuron signs, particularly in settings where degenerative and inflammatory causes have been excluded.