ABSTRACT: Hyperargininemia is a rare inborn error of metabolism due to arginase deficiency, which is inherited in an autossomal recessive manner. Arginase is the final enzyme of the urea cycle and catalyzes the conversion of arginine to urea and ornithine. This condition typically presents in early childhood (between 2 and 4 years of age) with developmental delay associated with progressive spastic paraparesis. Neonatal presentation is very uncommon with a poorly described outcome. Here, we discuss two cases of neonatal cholestasis as initial clinical presentation of hyperargininemia. In case 1, diagnosis was established at 2 months of age upon investigation of the etiology of cholestatic injury pattern and hepatosplenomegaly, and treatment was then initiated at when the patient was 3 months old. Unfortunately, the patient had progressive biliary cirrhosis to end-stage liver disease complicated with portal hypertension for which she underwent successful orthotopic liver transplant at 7 years of age. In case 2, hyperargininemia was identified through newborn screening and treatment was started when patient was 21 days old. Cholestasis was only identified in the patient's further evaluation and it resolved 2 weeks into treatment. The patient is currently 18 months old and her development and neurological examination remain unremarkable. Neonatal cholestasis as first presentation of hyperargininemia is rare, but this disorder should be included in the differential diagnosis of unexplained cholestasis in the neonate. In fact, these two cases suggest that arginase deficiency may be the cause of cholestatic liver disease.
Journal of Inherited Metabolic Disease 01/2011; · 3.58 Impact Factor