Late-Onset Ornithine Transcarbamylase Deficiency: Treatment and Outcome of Hyperammonemic Crisis

Abstract

Hyperammonemic crises in ornithine transcarbamylase deficiency (OTC) can be associated with devastating cerebral edema resulting in severe long-term neurologic impairment and death. We present an 8-year-old boy who had late-onset OTC deficiency in which early and aggressive management of hyperammonemia and associated cerebral edema, including therapeutic hypothermia and barbiturateinduced coma, resulted in favorable neurologic outcome. Our patient presented with vomiting and altered mental status, and was found to have a significantly elevated serum ammonia level of 1561 mmol/L. Hyperammonemia was managed with hemodialysis, 10% sodium phenylacetate, 10% sodium benzoate, L-arginine, intravenous 10% dextrose, intralipids, and protein restriction. He developed significant cerebral edema with intracranial pressures .20 mm Hg, requiring treatment with 3% saline and mannitol. Despite this treatment our patient continued to have elevated intracranial pressures, which were treated aggressively with non-conventional modalities including therapeutic hypothermia, barbiturate-induced coma, and external ventricular drainage. This therapy resulted in stabilization of hyperammonemia and resolution of cerebral edema. Molecular testing later revealed a hemizygous mutation within the OTC gene. Neuropsychological testing 1 year after discharge showed normal intelligence with no visualmotor deficits, minor deficits in working memory and processing speed, and slightly below average processing speed and executive functioning. Pediatrics 2014;133:e1072-e1076 Dr Bergmann conceptualized the case report, drafted the initial manuscript, and critically reviewed and revised the manuscript; Dr McCabe coordinated data collection and critically reviewed and revised the manuscript; Dr Smith critically reviewed and revised the manuscript; Dr Guillaume provided expertise in neurosurgical management and critically reviewed and revised aspects of the manuscript pertaining to neurosurgical intervention; Dr Sarafoglou provided expertise in endocrine and metabolic management and critically reviewed and revised aspects of the manuscript pertaining to endocrine and metabolic intervention; Dr Gupta conceptualized the case report and critically reviewed and revised the manuscript with emphasis on aspects pertaining to critical care medicine; and all authors approved the final manuscript as submitted.www.pediatrics.org/cgi

Fatal Nonhepatic Hyperammonemia in ICU Setting: A Rare but Serious Complication following Bariatric Surgery

“…Urea cycle disorders (UCDs), as a result of deficiency of or defects in enzymes, usually present with hyperammonemia causing severe morbidity and mortality [ 14 ]. Literatures have shown a manifestation of late onset of one or more enzyme functional deficiency/ies unmasking the genetic disorders of the urea cycle in patients after bariatric surgery [ 15 – 18 ]. Markedly increased plasma glutamine, ornithine, and urinary orotic acid levels in the background of severe malnutrition and zinc deficiency may have led to unfolding of the functional deficiency of urea cycle enzyme/s leading to impaired ureagenesis and intractable hyperammonemia.…”

Genomic Sequencing Expansion and Incomplete Penetrance

“…Many X-linked conditions can have variable penetrance also. These conditions are classically known to manifest in male individuals, 6 but symptoms can range widely in female individuals. Female individuals may be asymptomatic carriers, or they may be significantly affected by an X-linked condition.…”

Successful Management of Ornithine Transcarbamylase Deficiency Presenting with Reversible Metabolic Stroke in a Child

“…Mortality and morbidity rates are high in hyperammonemic encephalopathy in children with OTC deficiency, so aggressive management should be prompt as the prognosis is strongly influenced by the duration of the coma and peak ammonia levels. Long-term management with arginine and L-citrulline supplementation is debated to help to decrease the frequency of attacks and improve physical growth (13,14). Consequently late-onset OTC deficiency should be considered in the differential diagnosis of stroke, which is a rare presentation of a treatable disorder and early diagnosis can prevent a fatal outcome.…”