Two novel mutations in the L ferritin coding sequence associated with benign hyperferritinaemia unmasked by glycosylated ferritin assay.

Investigating persistent hyperferritinaemia without apparent iron overload is challenging. Even when inflammation, cirrhosis, Still's disease, fatty liver and malignancy are excluded, there remains a group of patients with unexplained hyperferritinaemia for whom rare forms of haemochromatosis (ferroportin disease) are a consideration. Preliminary results suggest that abnormal percentage glycosylation of serum ferritin is seen in some cases of genetically determined hyperferritinaemia. Serum ferritin is normally 50-81% glycosylated, but low glycosylation (20-42%) prevails in hereditary hyperferritinaemia cataract syndrome. This contrasts with hyperglycosylation (>90%) associated with the benign hyperferritinaemia related to missense L ferritin (p.Thr30Ile) mutation. Here, we describe two novel missense L ferritin variants also associated with hyperglycosylation, p.Gln26Ile and p.Ala27Val. Ferritin glycosylation, a comparatively simple measurement, can identify patients for DNA sequencing as hyperglycosylation (>90%) is associated with benign hyperferritinaemia and mutant L ferritin chain.

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.

Hypokalaemic rhabdomyolysis.

Hypokalaemic rhabdomyolysis is unusual, but the association between hypokalaemia and rhabdomyolysis can be overlooked if intracellular potassium leakage normalizes serum potassium by the time of presentation. This report describes a patient who presented with severe pain due to non-traumatic rhabdomyolysis and was found to have serum potassium of 1.4 mmol/L; magnesium 0.40 mmol/L; phosphate 1.40 mmol/L; adjusted calcium 1.87 mmol/L and creatine kinase 6421 U/L. In this case, intervention occurred before rhabdomyolysis could progress to the stage at which serum potassium may have self-corrected. This patient's hypokalaemia was at first refractory to treatment with potassium chloride, possibly due to coexisting magnesium deficiency. Initially, the patient denied alcohol abuse, but later admitted alcohol misuse prior to withdrawal three days before presentation. Hypokalaemia is associated with alcohol misuse, but abrupt withdrawal may exacerbate hypokalaemia and hypomagnesaemia. Acute or chronic myopathy is common in alcoholics due to alcohol toxicity and paradoxically the risk of rhabdomyolysis may be increased during periods of abrupt alcohol withdrawal.

Conjugated bilirubin measurements in Gilbert's syndrome: method dependence.

BACKGROUND: Introducing new methodology often requires alteration to reference ranges and may cause inconvenience. Reagent suppliers may not have validated reference ranges quoted in their method sheets. When ratios of analytes are important, as for conjugated and unconjugated bilirubin, the combined changes can cause confusion. METHODS: The effect on bilirubin result interpretation following a change from Vitros (E950) dry slide technology to the Bayer ADVIA 1650 wet chemistry system was studied. RESULTS AND CONCLUSION: Over-estimation of conjugated bilirubin without an appropriate reference range can cause interpretative confusion. It is important to identify key patient groups likely to be affected by method changes well in advance. These need to be worked up in addition to reference range checks. It is unwise to rely on manufacturers for advice in this area. This report gives conjugated or direct bilirubin and total bilirubin values obtained using the above methods in nine patients with Gilbert's syndrome.