Is More Effective Newborn Screening for Homocystinuria on the Horizon?

In 1963, two sisters from Northern Ireland with mental deficiency and seizures were discovered to have homocystine in their urine (1). In addition to the mental deficiency and seizures, these sisters had dislocated ocular lens (ectopia lentis), malar flush, genu valgum, and pes cavus, all features now known to be characteristic of classic homocystinuria (HCU) (2). This discovery was of particular significance because HCU was the first amino acid metabolic disorder discovered that closely resembled phenylketonuria (PKU), the prototypical metabolic disorder that had been described almost 30 years earlier as the first biochemical cause of mental deficiency. Although other amino acid disorders were described before HCU (1), they either presented clinically in the newborn or had much less clinical import, whereas those with HCU, like PKU, are normal until several months of age when irreversible developmental delay is apparent and subsequently mental deficiency appears. HCU differs from PKU, however, in that the clinical complications in HCU include somatic features, whereas in PKU the effect is exclusively mental deficiency. In HCU these somatic features resemble Marfan syndrome (3).