Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years.

OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.

Use of sapropterin dihydrochloride in maternal phenylketonuria. A European experience of eight cases.

Sapropterin dihydrochloride (SD) is the first drug treatment for phenylketonuria (PKU), but due to the lack of data, its use in maternal PKU must be undertaken with caution as noted in the FDA and EMEA labels. We collected data from eight pregnancies in PKU women treated with SD and we analysed the phenotypes of these patients, their tetrahydrobiopterin (BH4) responsiveness, the indications for SD treatment, the efficacy (metabolic control, phenylalanine (Phe) tolerance and offspring outcome) and the safety data. Results showed that in the seven patients known to be responsive to BH4, the use of SD during pregnancy was efficient in terms of metabolic control and Phe tolerance. The indications for giving SD included the failure of the low-Phe diet (n = 3), the fact that some of these women had never experienced the low Phe diet (n = 2), one unexpected pregnancy in a woman currently on SD and one pregnancy where the foetus was known to have PKU. The offspring of these seven pregnancies were all normal babies with normal birth measurements and outcomes. No side effect related to SD was observed in these seven cases. In the eighth case, SD was prescribed as a rescue treatment without previous knowledge of the BH4 responsiveness to a woman who was already 8 weeks pregnant without diet. The birth occurred at 33 weeks of gestational age with Potter syndrome (probably related to the absence of metabolic control during the first trimester) and the baby died in the first hours of life. In conclusion, the data presented here provides the first evidence that treatment with pharmacological doses of SD appears to be efficient and safe in women with PKU during pregnancy. Its use should, however, be restricted to those women previously identified to be clear responders to BH4.