Acute Encephalopathy in an Otherwise Normal Child - Enigma and Solution

A 7-year-old otherwise healthy male was admitted for encephalopathy. Few hours prior to admission, after waking up from an afternoon nap, he developed agitation and confusion, including leaving his shoes in the synagogue, ignoring his parents and unexplained crying outbursts. No recent fever, drug/medication exposure or head trauma. The mother reported an introvert "slow" child who avoids meat. Family history was non-contributory.

In the ER, He was alert, with normal vital signs, but did not communicate, mumbling meaningless words. On physical exam - no meningeal signs, no signs of trauma. Neurologic examination was limited due to poor cooperation but showed slightly dilated pupils that were equal and reactive and a nonspecific abnormal gait - with no further findings.

Initial workup included glucose, CBC and SMAC, blood cultures, blood gases, ammonia, coagulation profile, thyroid function, autoimmune encephalitis panel, LP, urine tests, ECG, Head CT. The only abnormal results were high ammonia level 500 µg/dL (norm: 30-125 µg/dL) and low levels of Vitamin B12 and folic acid. He received sodium benzoate and subsequently his mental status returned to baseline. Later, urine orotic acids, citrulline, and plasma amino acids were supportive of a diagnosis of ornithine transcarbamylase (OTC) deficiency.

OTC deficiency, the most common form of urea cycle defect, is a severe, X-linked recessive disorder affecting mostly males. The disease typically presents in the first month of life with life-threatening hyperammonemia in males, however, late-onset OTC has rarely been described. High-protein food aversion often develops in patient to protect them from ammonia load.