Neurological outcome of patients with ornithine carbamoyltransferase deficiency

Abstract

Background: Ornithine carbamoyltransferase (OCT) deficiency is the commonest of the inherited urea cycle disorders.

Aims: To determine the long term neurological and cognitive outcome of continuously treated surviving patients.

Methods: Twenty eight surviving children (five boys) with OCT deficiency who had been treated continuously with a low protein diet and alternative pathway therapy were identified. Those aged 5-16 years had a detailed neurological examination and psychometric testing.

Results: Four presented in the neonatal period and four were treated prospectively following antenatal diagnosis. Median (range) age at diagnosis for the later onset group was 19 (2-144) months; median time between onset of symptoms and diagnosis was 10 (2-48) months. Nine children had had less than three episodes of hyperammonaemic encephalopathy, the others more. Seven had focal abnormalities on neurological examination; 14 had global cognitive impairment; four had a normal IQ but specific learning difficulties. Sixteen underwent neuroimaging which was normal in three, showed focal abnormalities of the cerebral hemispheres in six, and global cerebral atrophy in seven.

Conclusion: Eighteen of 28 surviving children with OCT deficiency had disabling neurological complications. Plasma ammonia at diagnosis was the only factor that predicted this outcome. While most neurological complications could be attributed to hyperammonaemic encephalopathy, other mechanisms may also contribute to the neurological abnormalities.

Figure 1

The urea cycle and the uridine synthesis pathways. PRPP, phosphoribosyl pyrophosphate. Solid block shows the site of the missing enzyme in OCT deficiency.