The confusion between the diagnosis of Marfan syndrome and that of homocystinuria has been known since the classic report of Schimke et al. from Johns Hopkins in 1965 (1), 2 years after homocystinuria was first described (2). Before the Johns Hopkins report, it was widely assumed that someone with ectopia lentis and long extremities almost certainly had Marfan syndrome. The Johns Hopkins report drastically changed this assumption. Having become aware of the similarities between Marfan syndrome and this recently discovered inborn error of metabolism, homocystinuria, the Johns Hopkins group screened urine samples from patients with ectopia lentis and/or other features of Marfan syndrome and found that 38 of the patients (from 20 families) had homocystinuria, not Marfan syndrome. The clinical case study described in this issue is an excellent illustration of the need to differentiate these 2 genetic disorders.
Because the Marfanoid habitus may be present in patients with Marfan syndrome and those with cystathionine β-synthase deficiency, diagnostic mistakes continue in the medical community. Keeping in mind several key facts will minimize this confusion: (a) Atherosclerotic cardiovascular disease and venous/arterial thrombi and emboli are key elements in homocystinuria (3) but are absent as primary features of Marfan syndrome; (b) cognitive impairment may occur in patients with homocystinuria (3) but is not a feature of Marfan syndrome; and (c) aortic dilation is a cardinal feature of Marfan syndrome but is absent in children and young adults with homocystinuria.
The establishment of the correct diagnosis of homocystiniuria early in life is of paramount importance because a protein-restricted diet, vitamin B6, and/or betaine may eliminate the connective tissue and vascular complications, as well as death from a thrombosis or embolism. Some patients with homocystinuria may not manifest the classic phenotype (4). Thus, all patients with evidence of vascular disease at a young age should undergo testing to determine the concentration of total homocysteine in serum.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication August 24, 2010.
- Accepted for publication August 31, 2010.
- © 2010 The American Association for Clinical Chemistry