Successful Early Management of a Female Patient With a Metabolic Stroke Due to Ornithine Transcarbamylase Deficiency Albina Tummolo, MD, PhD,* Vito Favia, MD,* Rosa Bellantuono, MD,Þ Vito Bellino,Þ Antonio Ranieri,Þ Amelia Morrone, PhD,þ Tommaso De Palo, MD,Þ and Francesco Papadia, MD* Background: Ornithine transcarbamylase deficiency (OTC-D) is a urea cycle disorder caused by dysfunction of ornithine transcarbamylase, which frequently leads to hyperammonemia. Hyperammonemia repre- sents a medical emergency requiring prompt treatment to reduce plasma ammonia levels and prevent severe neurological damage, coma, and death, particularly in patients with acute decompensation-related coma. The clinical symptoms of OTC-D can manifest themselves either at an early stage, which is often associated with severe symptoms, or in later life (late-onset OTC-D), when symptoms may be less severe. There is currently little agreement over diagnostic signs of the condition or the most appropriate therapeutic approach. Hyperammonemia is usually treated with ammonia scavengers, continuous venovenous hemodialysis, and dietary changes. N-carbamylglutamate is approved for the treatment of hyperammonemia in N-acetylglutamate synthetase deficiency and may have efficacy in other urea cycle disorders. Methods/Results: Here, we report a 13-year-old girl who was diag- nosed with OTC-D at the age of 3 years. On this occasion, the patient presented with vomiting, lethargy, and mental confusion. Despite bio- chemical parameters being within normal ranges, she was comatose within a few hours. She was promptly treated with a combined therapy of contin- uous venovenous hemodialysis and N-carbamylglutamate, resulting in a gradual normalization of clinical symptoms within 30 hours. No neuro- logical damage was apparent at 18 months after treatment. Conclusions: This case demonstrates that clinical benefits can be obtained by beginning aggressive treatment of OTC-D within a few hours of the onset of severe neurological symptoms even in the ab- sence of altered biochemical markers. Key Words: ornithine transcarbamylase deficiency, urea cycle disorder, metabolic stroke (Pediatr Emer Care 2013;29: 656Y658) T he hepatic urea cycle represents the most effective meta- bolic pathway for clearance of ammonia generated from protein catabolism, through its conversion into urea and sub- sequent excretion in urine. Defects in any of the urea cycle enzymes can lead to failure of the urea cycle and hyperammo- nemia. Disruption of this pathway results in rapid development of symptoms associated with hyperammonemia, such as leth- argy, irritability, coma, and even death if left untreated. 1 Ornithine transcarbamylase deficiency (OTC-D) is the most common urea cycle disorder 2 and is an X-linked hereditary dis- order caused by defects in ornithine transcarbamylase (OTC). Infants with OTC-D often appear symptom free at birth but rapidly develop cerebral edema and related signs of leth- argy, anorexia, hyperventilation, hypothermia, seizures, neuro- logical posturing, and coma. 3 In other patients, such as male patients with a partial OTC defect and heterozygous females, symptoms of OTC-D may be less severe and may not manifest until later in life. 4Y6 However, acute decompensation episodes, triggered by events such as high protein intake and/or infec- tious damage, can elicit rapid onset of clinical symptoms, which may lead to coma and death within a few days in all patients if left untreated. 7 The primary goal in the treatment of OTC-D is to rapidly and effectively decrease acute hyperammonemia and to prevent recurrent hyperammonemia to avoid the associated irrevers- ible neurological complications. The early identification of clini- cal symptoms of OTC-D and rapid initiation of an appropriate therapeutic approach are therefore essential for effective man- agement of the condition. Traditionally, hyperammonemia has been treated with ammonia scavengers (sodium benzoate and sodium phenylbutyrate), hemodialysis, and a protein-restricted diet to rapidly reduce plasma ammonia levels. 8 We report the case of a 13-year-old female patient who had previously been diagnosed with OTC-D at the age of 3 years and had shown a good compliance to the therapeutic regi- men during the follow-up period. Genetic testing confirmed the presence of a mutant OTC gene (c.[803T9C] leading to p.[M268T] amino acid change). On this occasion, she presented with acute metabolic decompensation. The combination of stan- dard therapy, continuous venovenous hemodialysis (CVVHD) and N-carbamylglutamate (NCG) effectively reduced levels of ammonia, resulting in normalization of the clinical symptoms. Follow-up at 18 months indicated that she had sustained no neu- rological damage. CASE The patient was admitted to our unit after 2 days of nau- sea, vomiting, and lethargy. On admission, routine blood chem- istry tests were performed. These revealed a higher than normal ammonemia level (326.9 Hg/dL; normal value, 31Y123 Hg/dL), moderate hypertransaminasemia (aspartate aminotransferase, 45 U/L; alanine aminotransferase, 45 U/L; normal value, 10Y31 U/L), and normal kidney function. Both urine orotic acid and glutamine levels were within the normal range. Laboratory tests for infectious diseases, such as liver viral infections, markers of the TORCH complex and common agents of gastroenteritis were all negative. The patient was treated with 4% sodium benzoate (250 mg/ kg) and a bolus of bioarginine hydrochloride (250 mg/kg), resulting in the stabilization of ammonemia levels. The patient was then ILLUSTRATIVE CASE 656 www.pec-online.com Pediatric Emergency Care & Volume 29, Number 5, May 2013 From the *Metabolic Diseases and Clinical Genetics Unit, and †Paediatric Nephrology and Dialysis Unit, Children’s Hospital Giovanni XXIII, Bari; and ‡Metabolic and Muscular Unit, Paediatric Neurology, AOU Meyer, Meyer Children’s Hospital, Florence, Italy. Disclosure: The authors declare no conflict of interest. Reprints Albina Tummolo, MD, PhD, Metabolic Diseases and Clinical Genetics Unit, Children’s Hospital Giovanni XXIII, Via Amendola, 207 70127, Bari, Italy (e-mail: albinatummolo@yahoo.it). Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0749-5161 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.