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Answers to Epilogue questions
  1. Vivek Mundada1,
  2. Deepa Krishnakumar1,
  3. Manali Chitre1,
  4. Tilak Das2
  1. 1Department of Paediatric Neurology, Addenbrooke's Hospital, Cambridge, UK
  2. 2Department of Radiology, Addenbrooke's Hospital, Cambridge, UK
  1. Correspondence to Dr Vivek Mundada, Department of Paediatric Neurology, Addenbrookes Hospital, Cambridge CB2 0QQ, UK; v.mundada{at}

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Question 1: C

Unenhanced CT examination of the brain revealed extensive thrombosis in the superior sagittal, straight and left transverse sinuses (figure 1). The CT angiogram (figure 2) confirmed venous thrombosis and an arterial infarct. It revealed complete occlusion of left internal carotid artery and segmental vasculopathy, affecting multiple intracranial and extracranial vessels of both the anterior and posterior circulation along with an aneurysmal ascending aorta. The contrast-enhanced CT scan demonstrated a filling defect of the superior sagittal sinus with minimal peripheral contrast enhancement, known as the ‘empty delta sign’.1 It is a useful radiological sign with which the de novo diagnosis of sagittal sinus thrombosis could be made.

Question 2: D

Further metabolic investigations confirmed the diagnosis of homocystinuria as he had raised plasma homocysteine and methionine.

Homocysteine is a sulfur-containing amino acid produced in the metabolism of the amino acid methionine. In the liver cells, homocysteine can irreversibly enter the transsulfuration pathway (catalysed by vitamin B6) to produce the amino acid cysteine. If homocysteine does not enter the transsulfuration pathway, it can be converted back to methionine by the addition of a methyl group. Inherited homocysteinurias may be due to defects in the transsulfuration pathway (as in our case) or remethylation pathway (cobalamin and methylenetetrahydrofolate reductase defects).

Cardinal laboratory features in transsulfuration disorders are markedly increased plasma concentrations of homocysteine, total homocysteine, mixed homocysteine disulfides, methionine and urine homocysteine. In comparison, remethylation disorders have low-normal methionine levels and require supplementation of this amino acid as well as other vitamins.

Classical homocystinuria (type 1) is an autosomal recessive condition caused by deficiency of cystathionine β-synthase (CbS), affecting conversion of methionine to cysteine.2 The reported incidence of CbS deficiency is 1 in 344 000.

Serious manifestations of type 1 homocystinuria are one or more of features of deep-vein thrombosis of leg, cerebrovascular accidents, pulmonary embolism and occlusion of peripheral arteries, which needs to be recognised and treated early. The combination of thromboembolic episodes in a young person along with marfanoid habitus, myopia, ectopia lentis and learning disability are clues to the diagnosis of homocystinuria.3 ,4 Vascular form of Ehlers–Danlos syndrome usually causes arterial ischaemic stroke and arterial dissections without venous thrombosis, with normal plasma homocysteine and methionine.

Question 3: D

An early diagnosis is important as early dietary changes and medications can reverse oculocutaneous changes, prevent neurological impairment and stop progression of the disease.5 Almost half of the affected individuals with transsulfuration disorders respond to pyridoxine. In non-responders to pyridoxine, methionine-restricted, cysteine-supplemented diet, folic acid and betaine are the treatment options to lower disulfide metabolites.6



  • Contributors VM has prepared the manuscript of the article with the help of DK and MC. TD has helped in selecting the appropriate images required for this article.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.