Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

Is suboptimal phlebotomy technique impacting on potassium results for primary care?

BACKGROUND: Pre-analytical problems causing pseudohyperkalaemia have been highlighted previously. These include transit time and temperature effects when sample collection points are geographically widely spread. Similarly, inappropriate phlebotomy technique (in particular, requesting patients to fist clench to facilitate venesection) is a documented cause of pseudohyperkalaemia, but its incidence may be impossible to establish. This study illustrates how primary care population serum potassium data altered when local phlebotomy clinics optimized their technique. METHODS: The effect of improving phlebotomy was studied by plotting average monthly primary care population serum potassium data and average percentage of samples with hyperkalaemia (5.2 mmol/L or higher) against mean monthly temperature before and after changes in phlebotomy practice. Only samples from primary care were included between 2002 and 2005 inclusive. RESULTS: Primary care population serum potassium was inversely related to ambient temperature. Following the change in phlebotomy practice, the annual percentage of results above reference range (5.2 mmol/L or higher) was reduced from 9% to 6% and the number of results breaching the upper telephoning threshold (5.8 mmol/L or higher) fell from 0.9% to 0.5%. CONCLUSIONS: Ensuring that phlebotomists were trained to avoid facilitating venesection by requesting patients to hand grip (fist clench), was associated with lower mean serum potassium results for the primary care patient population and a reduced incidence of hyperkalaemia. It is likely that the contribution of patient fist clenching during phlebotomy to pseudohyperkalaemia has been underestimated.