Reversible Leukoencephalopathy with Acute Neurological Deterioration and Permanent Residua in Classical Homocystinuria: A Case Report

We report a 24-year-old patient with underlying classical homocystinuria who developed acute neurological deterioration apparently induced by malnutrition secondary to poor compliance with treatment and pancreatitis. Neurological examination revealed stupor, tremor of the upper extremities, spasticity, and Babinski responses of the bilateral lower extremities. The biochemical profile, including marked hypermethioninaemia, hyperhomocysteinaemia, and decreased cystine in plasma, is consistent with cystathionine β-synthase deficiency. Brain MRI showed reversible diffuse white-matter changes without evidence of thrombosis. The clinical features and neuroimaging including diffusion-weighted MRI suggest a demyelinating process similar to other inborn errors of the transsulfuration pathway such as methylenetetrahydrofolate reductase deficiency, disorders affecting methylcobalamin metabolism (cobalamin C, D, E, and G disorders), and methionine adenosyltransferase deficiency. She was left with residual spastic paraparesis despite normal follow-up MRI. Our observation suggests that reversible demyelination is another neurological manifestation of classical homocystinuria; however, the pathophysiology is unknown.