Marfan syndrome and classic homocystinuria represent the top 2 in the list of differential diagnoses for a patient presenting with external features of tall stature, disproportionately long limbs, arachnodactyly, scoliosis, and, after ophthalmologic investigation, lens dislocation. This case report is of an individual who carried the diagnosis of Marfan syndrome for a period of 30–40 years before the eventual recognition that she really was affected with homocystinuria due to cystathionine β-synthase deficiency.
Although we tend to regard the measurement of homocysteine as one of the more recent additions to clinical laboratory repertoires, methods for the measurement of free homocystine in the urine have been available for many years. It is not clear whether this particular patient was ever investigated for homocystinuria as a child. It may well be that inadequately sensitive colorimetric spot assays were available for investigation at the time and that homocystinuria was erroneously ruled out, leaving Marfan syndrome as a diagnosis of exclusion.
The case is an excellent example of how we should not label any patient for life with a genetically unproved condition, because medical knowledge expands and therapeutic modalities for the correct diagnosis frequently improve. Although these 2 conditions have a number of features in common, they differ appreciably in the cause of death. Marfan syndrome frequently causes aortic dissection, whereas homocystinuria leads to arterial or venous thrombosis. Appropriate and different medical monitoring is required.
The treatment options for the 2 conditions are also very different. Treatment for homocystinuria, including vitamin B6 therapy, is very effective in some patients and has been around for many decades. Additional therapeutic intervention may include betaine or dietary restriction of methionine. This particular patient appears to be biochemically responsive to vitamin B6, and earlier treatment might have alleviated some of the relentless disease progression. Therapy for Marfan syndrome is still experimental. Angiotensin antagonists such as losartan demonstrate promise in reducing aortic stress.
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Authors' Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: M.J. Bennett, Clinical Chemistry, AACC.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: None declared.
Expert Testimony: None declared.
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 11, 2010.
- Accepted for publication August 16, 2010.
- © 2010 The American Association for Clinical Chemistry