Novel liver findings in ornithine transcarbamylase deficiency due to Xp11.4-p21.1 microdeletion.

Abstract Ornithine transcarbamylase deficiency(OTCD, OMIM 311250), the most common urea cycle disorder, results in impaired synthesis of citrullinefrom carbamoyl phosphateand ornithine. Individuals have been identified with OTCD due to a contiguousgene deletion at Xp11.4-p21.1 and unique clinical features, described as the “extended OTCD phenotype”. We present a male with neonatal-lethal OTCD due to a 1.87 Mb microdeletion at Xp11.4-p21.1 (37126841-38998991 hg18). Autopsy revealed a novel histological finding of hepatocyte globular and granular inclusions. Such inclusions have not been described in OTCD or other metabolic disordersand are not an associated finding in neonatal liver failure due to other causes. The deleted region includes the gene SYTL5 , potentially involved in RAB27A- dependent membrane trafficking in the liver and placenta. We propose that the contiguousgene deletion could contribute to the severity of the clinical presentation here and hypothesize that deletion of SYTL5 could contribute to the liver findings.