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The Treatment of High Homocysteine Concentrations in Homocystinuria: Biochemical Control in Patients and Their Vascular Outcome

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Book cover Homocysteine and Vascular Disease

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 230))

Summary

The natural history of individuals with homocystinuria due to cystathionine β-synthase deficiency was first documented in 1985 by Mudd et al [1]. Untreated, these individuals have severe hyperhomocysteinemia resulting in complications involving the eye (ectopia lentis), skeletal (osteoporosis, dolichostenomelia), vascular (thromboembolic events) and central nervous systems. Vascular complications are, however, the most striking cause of major morbidity and mortality in homocystinuric individuals. The aims of treatment must be to prevent or ameliorate particularly these life-endangering events by controlling or eliminating the severe hyperhomocysteinemia. There are currently three recognized modalities of treatment. For the pyridoxine responsive individual, pyridoxine in pharmacological doses in combination with folic acid and vitamin B12 will correct the biochemical abnormalities. In pyridoxine-nonresponsive homocystinuria, a methionine restricted, cystine supplemented diet in combination with the use of pyridoxine, folic acid and vitamin B12 is the treatment. However, good compliance with the diet may be difficult to obtain particularly in the late-detected individuals. Betaine, a methyl donor, may be useful in these individuals or as an adjunct to such a diet. Additional medical measures that do not affect the biochemical abnormalities but aim at reducing or eliminating the thrombotic tendencies have also been used. These include dipyridamole, either alone or in combination with aspirin to normalise decreased platelet survival and minimise vascular intimal lesions, the avoidance of situations associated with an increased risk of thromboembolism and the use of high dose antithrombotic prophylaxis with heparin or warfarin in conditions with prolonged bedrest. From the data recently published by the centers treating a total of 84 homocystinuric individuals with 1314 patient-years of treatment in Australia [4], the Netherlands [5] and Ireland [6], 53 vascular events would have been expected if they had remained untreated according to the data of Mudd et al[1]. Instead only five have been recorded while on treatment (relative risk = 0.091 (95% CI 0.043–0.190); p<0.001). This clearly establishes that appropriate treatment of severe hyperhomocysteinemia significantly reduces the vascular risk in homocystinuria, albeit post-treatment homocysteine levels may still be several times higher than the cut-off point for homocysteine in the normal population. The present findings may have relevance to the current concept of mild hyperhomocysteinemia and its association with cardiovascular disease, in which the elevation of plasma homocysteine levels is considerably lower than the post-treatment levels reported by the three centers.

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  1. Godfried H. J. Boers
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  2. Sufin Yap
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  3. Eileen Naughten
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  4. Bridget Wilcken
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Editors and Affiliations

  1. Department of Cardiology, The Cleveland Clinic Foundation, Desk F15, 9500 Euclid Avenue, 44195, Cleveland, Ohio, USA

    Killian Robinson

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Boers, G.H.J., Yap, S., Naughten, E., Wilcken, B. (2000). The Treatment of High Homocysteine Concentrations in Homocystinuria: Biochemical Control in Patients and Their Vascular Outcome. In: Robinson, K. (eds) Homocysteine and Vascular Disease. Developments in Cardiovascular Medicine, vol 230. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1789-2_22

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