ESPE Abstracts

Background: Late-onset ornithine transcarbamylase deficiency (OTCD) is a clinical challenge due to its nonspecific symptoms and the potential for delayed treatment. Hyperammonemia caused by acute metabolism disorder leads to life-threatening encephalopathy. We presented a unique case of OTCD initially manifesting with hyperthyroidism, resulting in refractory hyperammonemia.

Case report: A previously healthy 14-year-old Chinese male presented to the emergency room with a 5-day history of intermittent vomiting and a 3-hour onset of altered consciousness. The patient's vomiting, occurring 3-5 times a day for 5 days, was not accompanied by any discomfort such as fever, abdominal pain, diarrhea, dizziness, and headache. Despite symptomatic treatment, vomiting persisted, and he developed irritability, blurred vision, and decreased consciousness shortly before admission. On physical examination, the patient have good growth and development, and the GCS score was 10. He exhibited low-grade fever and tachycardia. Mild exophthalmos and a slight enlargement of the thyroid gland were observed. Initial blood tests revealed a markedly increased plasma ammonia level of 331 umol/L, prompting immediate hemodialysis and arginine administration. Subsequent evaluations confirmed that he was suffered from Graves’ disease, evidenced by increased free T4 and T3 levels (FT3 17.01 pmol/L, FT4 68.90 pmol/L), suppressed TSH (TSH <0.01 mIU/L) and positive thyrotrophin receptor antibody (TRAB 14.13 IU/L). Treatment with methimazole, beta-blocker, and glucocorticoids was initiated. Although thyroid storm could partly account for his altered mental status, the etiology of hyperammonemia was elusive. After ruling out other hepatic disorders, a significant increase in urinary orotic acid suggested a urea cycle disorder, such as OTCD, leading to the addition of glyceryl phenylbutyrate to his regimen. Despite temporary reductions in plasma ammonia levels through hemodialysis, plasma ammonia levels invariably rebounded only few hours post-hemodialysis. Following four days of intermittent hemodialysis and concurrent medication, the patient's condition acutely deteriorated, presenting with irregular respiratory patterns, coma, and dilated pupils, culminating in death due to cerebral edema and herniation. Finally, the genetic analysis identified an OTC gene mutation (exon 8: c.817_819 del [p. E 273 del]), confirming the diagnosis of OTCD.

Conclusion: This report describes the first known case of late-onset OTCD case that started with hyperthyroidism. The metabolic stress induced by hyperthyroidism exacerbated the hyperammonemia, and made it more difficult to correct. Urea cycle disorders should be considered among elderly children with acute hyperammonemia, particularly in the context of metabolic stress. Continuous hemodialysis are crucial to prevent fatal brain herniation.