Inborn errors of urea synthesis

Abstract

Inborn errors of urea synthesis can present in the newborn period as a catastrophic illness or later in childhood or adulthood with an indolent course punctuated by hyperammonemic episodes. Because symptoms mimic other neuropsychiatric disorders, it is common for there to be a delay in diagnosis, often with dire consequences. Diagnosis relies on the combination of clinical suspicion and the measurement of ammonium, lactate, and amino acids in plasma and organic acids and orotic acid in urine. Treatment involves nitrogen restriction combined with the stimulation of alternate pathways of waste nitrogen excretion. More recently liver transplantation has been performed as enzyme replacement therapy. The outcome is poor in children who survive prolonged neonatal hyperammonemic coma, with most manifesting developmental disabilities. The etiology of neuronal injury in this disorder is unclear but may involve some combination of ammonia/amino acid accumulation, neurotransmitter alterations, and excitotoxic injury. Gene therapy holds the promise of improved treatment in the future.

In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.

“…2). Because of random inactivation of the X chromosome, female carriers for a sex-linked disorder such as OTC deficiency manifest a broad spectrum of phenotypes (24,25). Most remain asymptomatic, but even ostensibly "silent" carriers sometimes develop hyperammonemia during a period of stress (26).…”

Neurological implications of urea cycle disorders

“…1). These disorders may present at any age and the consequences are neurological and of varying severity (Table 1) (Bachmann 2003a;Batshaw 1994). Common to the majority of the UCDs is the presence of hyperammonaemia, and its effects on neurological functioning.…”

Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: A role for detailed molecular analysis in complex presentations of classical diseases

“…Ornithine transcarbamylase deficiency (OTCD; OMIM 311250), an X-linked disorder, is the most common inherited defect of ureagenesis, affecting 1:14,000 births [1]. Most mutations are 'private' single nucleotide substitutions or small insertions or deletions [2][3][4].…”