Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency.

ABSTRACT

In an expanded newborn screening program for inborn errors of metabolism by LC-MS/MS in Tuscany, six newborns out of 169,000 showed decreased blood citrulline levels. In one of them, molecular analysis of the OTC gene identified the known p.Trp265Leu mutation, which is correlated with late-onset ornithine transcarbamylase deficiency (OTCD). Hypocitrullinemia is not a reliable marker for OTCD newborn screening, especially for late-onset forms that may exhibit normal citrulline levels. However, when hypocitrullinemia is detected in a newborn in whom intestinal dysfunction and prematurity have been excluded, OTCD should be investigated first because of the OTCD incidence (114,000) and the small size of the OTC gene coding sequence.