Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings

SILVERA-RUIZ, SILENE M.; ARRANZ, JOSÉ A.; HÄBERLE, JOHANNES; ANGARONI, CELIA J.; BEZARD, MIRIAM; GUELBERT, NORBERTO; BECERRA, ADRIANA; PERALTA, FERNANDA; DE KREMER, RAQUEL DODELSON; LARÓVERE, LAURA E.

ORPHANET JOURNAL OF RARE DISEASES

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2019 vol. 14

1750-1172

ackground: The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina.Results: Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 ca