Increased Homocysteine in a Patient Diagnosed with Marfan Syndrome

Abstract

A 53-year-old Caucasian woman was diagnosed in late childhood with Marfan syndrome according to characteristic skeletal features and bilateral lens dislocation. In addition, she has a history of nonischemic cardiomyopathy with severe left ventricular failure and atrial fibrillation, diabetes mellitus type 2, hyperlipidemia, progressive dementia, numbness in the lower extremities, and hypothyroidism following thyroidectomy for thyroid cancer. Additional findings revealed in a physical examination included an upper-to-lower segment ratio of 0.88, an arm span–to–height ratio of 1.02 (an upper-to-lower–segment ratio 1.05 are 2 of the diagnostic criteria for Marfan syndrome), an elongated face, a high arched palate, and crowded dentition. She recently underwent further laboratory testing after a cardiologist did not find 2 characteristic features of Marfan syndrome, namely an enlarged aortic root and mitral valve prolapse. Her total plasma homocysteine and methionine concentrations were increased at 198 μmol/L (reference interval, 5–15 μmol/L) and 370 μmol/L (reference interval, 10–50 μmol/L), respectively. The patient's plasma homocystine concentration was 48 μmol/L (reference interval, <2 μmol/L), and her urine homocystine concentration was also markedly increased. These biochemical abnormalities are not characteristic of Marfan syndrome. Her diagnosis was reconsidered in light of these new data. In this case, a long-standing clinical diagnosis was inconsistent with recently obtained clinical and biochemical data. The biochemical data were virtually diagnostic of homocystinuria [OMIM3 (Online Mendelian Inheritance in Man) 236200], a term historically used to describe inborn errors of metabolism characterized by excessive excretion of homocystine in urine and high concentrations of total plasma homocysteine. Homocystinuria is most commonly caused by autosomal recessive inheritance of a deficiency in cystathionine β-synthase (CBS) activity (1). The worldwide incidence has been estimated to be between 1 in 200 000 and 1 in 335 000 population (2), with the highest incidence (1 in 1800) reported in Qatar …