Homocystinuria in adult patients

Classical homocystinuria is aminoacidopathy fi rst described in 1962. It results from the inability of degradation and consequential accumulation of the amino acid homocysteine in the circulation. Increased plasma/serum and urine homocysteine levels can be caused by diff erent inherited metabolic disorders or by some acquired conditions. Classical homocystinuria (McKusick 236200) is a pathologic condition that arises from elevated concentrations of homocysteine in the plasma, most frequently due to cystathionine β-synthase defi ciency (CBS; EC 4.2.1.22). If not treated in time, the disease can lead to serious central nervous system, eye, bone and blood vessel complications, mainly thromboembolism. However, newborn screening for homocystinuria is not routinely performed in many countries, including Croatia. In spite of various reasons that may cause delay in the diagnosis of homocystinuria, the predominant one is that physicians often fail to connect a cluster of common symptoms with this rare disease. Patients are referred to various specialists who focus on the treatment of diff erent clinical manifestations of homocystinuria, mostly without success. Without treatment of the underlying disease, chronic complications of homocystinuria progress and patients are jeopardized by sometimes even life-threatening thromboembolism. Patients with CBS defi ciency in whom typical clinical phenotype is absent, represent a particular diagnostic problem, as homocysteine is usually only periodically increased when pyridoxine is omitted from therapy. Within these patients recurrent episodes of thromboembolism are commonly the only clinical feature of homocystinuria. Based on our experience and data from the literature, early recognition of severe or rapidly progressing myopia, subluxation of ocular lenses, ‘marphanoid’ appearance and/or thromboembolism should be an indication for plasma homocysteine measurement and family screening.

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