Background: Inherited homocystinuria is a rare autosomal recessive metabolic disorder affecting several organs including the CNS resulting in a neurologic and vascular abnormalities through toxic effect of homocysteine. Neurologic involvement includes progressive mental retardation, seizure, dystonia, behavioral and personality disorder, while the vascular one include stroke due to thromboembolic syndromes.
Case report: A 6-year-old boy with learning disability, skeletal abnormalities,myopia,frequent fractures , and previous febrile convulsion presented with sudden onset of worsening headache ,left sided frequent seizures with generalization, and behavioral changes for 48 hours followed by abnormal gait, and deterioration in his mental status.Preceded by febrile illness.His parents were consanguineous with no neurologic disorder or epilepsy in the family. Examination revealed mental subnormality,poor social interaction, slurred speech, general hypotonia left > right,DTR+1 , extensor planter response bilaterally,and unsteady gait. Brain MRI and MRV showed extensive superior sagittal sinus thrombosis,localized cortical right parieto-occipital infarction,and abnormal white matter of both hemispheres,sparing subcortical fibers with diffusion restriction suggestive of metabolic white matter disease. Laboratory evaluation revealed, high serum methionine, homocysteine level,and presence of cysteine in the urine.Marked improvement was noted after intravenous anticoagulant therapy.He was maintained on lamotrigine ,aspirin, high dose of oral pyridoxine,folate ,betaine, and methionine-restricted diet. Genetic study revealed a nonsense homozygous mutation in CBS gene
( C969G>A P.Trp323Ter (W323X) ) . Afollow-up brain MRI showed a significant recanalization of all sinuses with reduction of thrombosis within the superficial cortical veins.
Conclusion:Although homocystinuria is a vanishing disease, physician should keep high index of suspicion among patients with mental disabilities and seizure disorders as early detection and treatment can prevent future neurologic and vascular complications.
Key words: Homocysteine, Cerebrovascular disease, Metabolic disorders, Seizure disorder