Late-onset of ornithine transcarbamylase deficiency: A rare medical examiner case

Abstract

Ornithine Transcarbamylase (OTC) is an enzyme of the urea cycle, which converts ammonia into urea in the liver cells. OTC plays a crucial role in the breakdown and removal of nitrogen in the body. OTC deficiency is a rare X-linked recessive disorder that classically presents in early life with signs of hyperammonemia and progressive central nervous system involvement resulting in seizures, coma, and death. Sentinel presentation in adulthood is quite rare. A 29-year-old man developed altered mental status after receiving an epidural steroid injection 3 days earlier for back pain. He presented to the emergency department severely agitated, and his workup revealed an elevated ammonia level of 125 µmol/L. He refused admission and was discharged against medical advice. The following day, his mentation deteriorated, he developed status epilepticus, and was transported to another emergency department. He was admitted with worsening hyperammonemia (levels rising to over 700 µmol/L). His clinical condition progressive deteriorated, and he developed encephalopathy and diffuse cerebral edema. Liver function testing indicated progressive liver damage, and amino acids were detected in his blood and urine. Clinical and laboratory findings suggested undiagnosed OTC enzyme deficiency. He died 2 days after admission. An autopsy showed an 1890 g liver with diffuse yellow discoloration and softening. Histology and electron microscopy revealed findings suggestive of urea cycle disorder, such as microvesicular steatosis, apoptosis, and scattered mitosis, clusters of clear hepatocytes at the PAS stain, and mitochondria abnormalities. Genetic analysis revealed a hemizygous pathogenic variant of the OTC gene (c.622G>A). OTC deficiency should be suspected in subjects with hyperammonemic encephalopathy. If a genetic mutation is identified in the deceased, surviving family members should be screened to prevent potential life-threatening complications.

Keywords: autopsy; forensic pathology; genetic testing; hyperammonemia; liver failure; ornithine transcarbamylase; urea cycle.