Reversible Cerebral White Matter Abnormalities in Homocystinuria

  • Naila IsmayilovaEmail author
  • Andrew D. MacKinnon
  • Helen Mundy
  • Penny Fallon
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)


Striking MRI brain changes resembling leukoencephalopathy are rarely seen in classical homocystinuria. Our case suggests that reversible white matter changes (WMC) are linked to elevated plasma methionine levels arising during treatment.

A 6-year-old boy with learning difficulties and a normal MRI brain scan was diagnosed with homocystinuria (initial total homocysteine 344 μmol/L and methionine 64 μmol/L). At the age of 6.5 years, he developed superior sagittal sinus (SSS) thrombosis. Antithrombotic and homocysteine-lowering treatments were started. Due to poor dietary compliance and betaine treatment, his methionine level reached 1,285 μmol/L, and left side weakness developed. Repeat MRI scan revealed new confluent WMC in previously myelinated brain areas. Further 3-month treatment with tighter dietary control significantly dropped his methionine level (233 μmol/L) with resolution of his neurological deficit and of radiological changes.

We suggest a reversible toxicity from hypermethioninaemia as a possible source of cerebral WMC (secondary to a demyelinating process) in patients with homocystinuria. It highlights the importance of homocysteine-lowering treatment as a prevention and complete resolution of neurological complications. It also demonstrates the need to consider homocystinuria in a differential diagnosis of paediatric leukoencephalopathy.


Betaine Homocystinuria Hypermethioninaemia White matter abnormalities 



Cystathionine beta-synthase


Intracranial pressure


5,10-Methylenetetrahydrofolate reductase


Superior sagittal sinus


White matter changes


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Naila Ismayilova
    • 1
    Email author
  • Andrew D. MacKinnon
    • 2
  • Helen Mundy
    • 3
  • Penny Fallon
    • 1
  1. 1.Department of Paediatric NeurosciencesSt George’s University Hospitals NHS Foundation TrustLondonUK
  2. 2.Department of Neuroradiology, Atkinson Morley Regional Neuroscience CentreSt George’s University Hospitals NHS Foundation TrustLondonUK
  3. 3.Department of Paediatric Inherited Metabolic DiseaseEvelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation TrustLondonUK

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