Ornithine Transcarbamylase Deficiency: A Possible Risk Factor for Thrombosis

We describe four infants with ornithine transcarbamylase (OTC) deficiency, who developed arterial and venous thromboses prior to undergoing liver transplantation. These patients prompted a retrospective chart review of children with inborn errors of metabolism associated with hyperammonemia seen at our institution between 1998 and 2008; no additional cases with thrombosis were detected. Data abstracted from medical records include patient demographics, details about thrombus, treatment, associated risk factors and metabolic abnormalities. OTC deficiency was diagnosed during the first week of life in all patients (median age – 4 days; age range 1–7 days). Thrombotic complications developed prior to liver transplant in all patients (median age - 63 days; age range 6–71 days). One patient had arterial thrombus; the rest developed venous thromboses. Possible risk factors for thrombosis are summarized in the table below.

Table 1. Patient characteristics that are potential risk factors for thrombosis * AT III - Anti-thrombin III

Multiple pro-thrombotic risk factors were present. Hyperammonemia was seen in 3 patients and low plasma arginine level was present in all patients around the time of thrombosis. As L-arginine is a substrate for nitric oxide synthesis, arginine deficiency leads to low nitric oxide levels. Recent studies have linked nitric oxide insufficiency to platelet hyperaggregability, thrombosis and endothelial damage. Infants with OTC deficiency, indwelling vascular catheters, hyperammonemia and low plasma arginine may be at increased risk for thrombosis. Further studies in patients with OTC deficiency, to evaluate the role of hyperammonemia and low plasma arginine in thrombogenesis are warranted.