Late onset heterozygous ornithine transcarbamylase deficiency mimicking complex partial status epilepticus

Abstract

A 57 year old woman with post-traumatic complex partial seizures was admitted because of recurrent episodes of altered mental state over the preceding 4 years, each lasting up to 5 days. There was a history of dietary protein intolerance since childhood and two of her daughters had died in the neonatal period from unexplained encephalopathies. In hospital she developed fluctuating confusion, amnesia, and sudden episodes of unresponsiveness. An EEG was consistent with complex partial status epilepticus but there was no response to benzodiazepines. Nasogastric feeding and sodium valproate were given and shortly afterwards she lapsed into a deep coma. Blood ammonia and urinary orotate were raised, and genetic testing confirmed that she was a carrier of a mutation in exon 3 of the ornithine transcarbamylase gene (C to T at position 92). Treatment with protein restriction, carnitine, and sodium phenylbutyrate led to a full recovery over a period of 3 months. To our knowledge this is the oldest age of onset yet described in a manifesting carrier. She is the fifth patient with heterozygous ornithine transcarbamylase deficiency reported to have had a severe reaction to sodium valproate. Hyperammonaemic encephalopathy should be considered in patients of any age who experience fluctuating confusion. (J Neurol Neurosurg Psychiatry 2000;69:813-815)

Neurological implications of urea cycle disorders

“…In addition, EEG abnormalities have been reported in infants with OTCD in the absence of clinical seizures (Bogdanovic et al 2000;Brunquell et al 1999;Engel and Buist 1985;Verma et al 1984) and may be used to explain differential responses to intervention and outcome when the clinical examination appears similar. EEG patterns that fail to respond, either in amplitude or frequency, to noxious, auditory, or visual stimuli predict a poor prognosis for meaningful neurological recovery, whereas similar patterns with preserved reproducible reactivity imply the potential for some recovery and should be compared with recordings repeated several days laFter.…”

“…An EEG can also detect anomalies in adults with partial-onset disease who often present with psychiatric features, but in fact may have complex partial status epilepticus revealed by continuous semi-rhythmic sharp wave discharges as the cause of the encephalopathy (Bogdanovic et al 2000).…”

Non-Hyperammonemic valproate encephalopathy

“…2 underlying urea cycle enzyme deficiencies may predispose to valproate-induced hyperammonemia. 5 The risk factors included high initial dose 1 , long-term valproate therapy 2 , and long-term valproate therapy with concomitant topiramate. 2 …”

Young-Onset Dementia

“…A fluctuating level of cognitive function may be suggestive of DLB, 37 recurrent complex partial seizures, 4 paroxysmal cardiac arrhythmia, 38,39 remitting and relapsing inflammatory condition such as multiple sclerosis, 40 VGKCAb, 7 recurrent exposure to toxins such as alcohol 41 or recreational drugs, 42 an intermittent metabolic disturbance such as recurrent hypoglycemic episodes in treated poorly controlled diabetes mellitus (DM) or due to insulinoma, 43 hyperammonemic encephalopathy due to liver disease, 44 ureterosigmoidostomy, 45 valproate therapies, 45 ornithine transcobalamine deficiency 46,47 or citrullinemia (argininosuccinate synthetase deficiency), 48 pancreatic encephalopathy, 49 porphyria, 50 or recurrent hypoxia in the context of obstructive sleep apnoea. 51 Anxiety, depression, 52 and conversion disorders 53 may also cause a variable cognitive function.…”