User login

We offer our registered users tailored information, free online courses and exclusive content.

You have an old EXCEMED account ...

Our platform has been renewed. All users registered at any of the old websites are kindly requested to reset their password. Why is this?

... or you lost your password?

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Frequency of blood phenylalanine monitoring and point-of-care home blood phenylalanine monitoring devices

Frequency of blood phenylalanine monitoring and point-of-care home blood phenylalanine monitoring devices

Blood phenylalanine (Phe) remains the acknowledged biochemical marker for monitoring treatment outcome in patients with phenylketonuria (PKU). In many European centres, blood Phe monitoring is usually conducted by either blood spots collected at home by patients or caregivers which are sent to hospital laboratories, or alternatively, by venous blood samples taken in hospital clinics. Patients with PKU require regular and consistent blood Phe monitoring throughout life, with patients/caregivers receiving timely feedback about blood Phe results and their level of overall metabolic control. The European PKU guidelines1 recommended that blood Phe measurements are conducted weekly in infancy, fortnightly in children aged 1 to 12 years, monthly in those over 12 years of age and twice weekly during pregnancy.

Little research has been conducted on the optimal frequency of monitoring, however it is likely that attentive and regular blood Phe monitoring will be associated with better control. Waitzman et al2 found that each week of delay in blood Phe sampling in children with PKU aged ≤8 years was associated with a 10% reduction in the likelihood that a subsequent reading would fall below the upper target range. In a longitudinal, retrospective study from Chile, Garcia et al3 found that a lower number of blood Phe monitoring samples was linked with poor Phe control. They identified an associated between fewer blood samples taken during the second year of life with a discontinuation of diet at a later age. It has been reported that some parents ‘prepare’ for the blood Phe test just before it is due – almost half of Utah families (47%) in a study altered their eating behaviour prior to a blood test.4 Unfortunately, research indicates that patient adherence with blood Phe monitoring decreases with age. Jurecki et al5 established that 37% of patients aged ≥30 years checked their blood Phe concentrations once a year or less and 31% of adolescents aged 13 to 17 years measured blood samples only once or twice a year.

Some of the disadvantages associated with home blood spot monitoring are:

  1. The slow turnaround of results - it may take up to two weeks for patients/caregivers to receive their blood Phe results in some areas
  2. The cost of blood spot postage and analysis by either tandem mass spectrometry, amino acid analysers or high-performance liquid chromatography, particularly if additional blood spot samples are collected
  3. The quality of blood spots may be unsatisfactory e.g. small blood sample, double ‘spotting’ of blood on cards
  4. Phe analysis from dried blood spots is 8–26% lower than from venous blood samples1
  5. Home blood spot monitoring may only be available in developed rather than developing countries.

Therefore, a ‘point-of-care’ home monitoring machine able to measure blood Phe levels with accuracy (both at low and high blood Phe concentrations), that is robust and easy to operate is a priority. This should widen the accessibility of home Phe monitoring to patients in less developed countries and enable patients and their caregivers to manage PKU more effectively. It should enable more frequent testing and provide more timely feedback. For example, when managing maternal PKU, a home Phe monitor may give more information about blood Phe variability during the day, the impact of morning sickness and the effect of poor energy intake. This will permit more timely adjustments to be made to the diet. It may help adults with PKU understand the impact of food socialisation (e.g. eating extra protein when in restaurants or holidays) and help them to identify the most effective corrective action themselves. When parents realise that children have eaten ‘forbidden food,’ the ability to perform some serial blood Phe measurements to ensure that blood Phe levels return to target levels quickly would be very reassuring and save them considerable anxiety waiting for the next blood Phe result to be returned from the hospital laboratory. It would also provide great insight about the impact of illness; currently the effect of each infection on blood Phe control appears to vary between and within patients.

Over recent years there has been much development to produce a ‘point-of-care’ machine that can be used to assess blood Phe in the home. Many prototypes have been designed but there are no published results describing their efficacy in patients with PKU. Before any ‘point-of-care’ machine can be launched, it will require systematic and structured premarketing evaluation to provide supporting evidence for regulators and national reimbursement systems. There appear to be many hurdles to overcome before ‘point-of-care’ blood Phe analysis machines are established as part of routine care, but we should continue to strive for this development as this tool could assist patients and caregivers in achieving significantly better blood Phe control.


  1. van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis 2017 Oct 12;12(1):162.
  2. Waitzman NJ, Bilginsoy C, Leonard CO, et al. The effect of phenylalanine test frequency on management of phenylketonuria (PKU). University of Utah, 2004.
  3. García MI, Araya G, Coo S, et al. Treatment adherence during childhood in individuals with phenylketonuria: Early signs of treatment discontinuation. Mol Genet Metab Rep 2017 Apr 28;11:54-58.
  4. Bilginsoy C, Waitzman N, Leonard CO, Ernst SL. Living with phenylketonuria: perspectives of patients and their families. J Inherit Metab Dis 2005;28(5):639-49.
  5. Jurecki ER, Cederbaum S, Kopesky J, et al. Adherence to clinic recommendations among patients with phenylketonuria in the United States. Mol Genet Metab 2017 Mar;120(3):190-197.

Anita Macdonald

Dietetic Department
The Children’s Hospital
Birmingham, United Kingdom
home blood PHE monitoring
monitoring devices