Three-year audit of the hyperphenylalaninaemia/phenylketonuria spectrum in Victoria.

Aims: To determine the prevalence, the types and severity of hyperphenylalaninaemia (including phenylketonuria (PKU)) in Victoria and to report on a new treatment modality of PKU.

Methods: We reviewed the medical records of all patients diagnosed with high blood phenylalanine levels by newborn screening between November 2001 and October 2004.

Results: We identified 17 newborn babies with high levels of blood phenylalanine (total samples: 190,835). Dihydrobiopterin reductase deficiency was excluded in all babies. Five babies had persistent phenylalanine levels of 200-300, and do not receive any dietary or pharmaceutical therapy. One baby was diagnosed as having pyruvoyl tetrahydro-pterin synthase deficiency. Following reports of tetrahydrobiopterin (BH(4))-responsive PKU, we have performed a BH(4) load (20 mg/kg, 6R-5,6,7,8-tetrahydro-L-biopetrin dehydrochloride; Schricks Laboratories, Jona, Switzerland) in 10 newborn babies with PKU (one baby with a phenylalanine level of 2600 micromol/L was started on diet without prior load). Three babies had a significant response to BH(4) (>35% decrease in phenylalanine level). Protein restriction (1.2 g/kg/day) and introduction of phenylalanine-free formula, in addition to BH(4) treatment, were necessary in one patient. The other patients maintain good metabolic control with BH(4) treatment only (at approximately 11 mg/kg/day) and an intake of 2-3 g protein per day. Of the nine babies who are on a full PKU diet, three have high phenylalanine tolerance (consistently >40 mg/kg/day).

Conclusion: There is a spectrum of severity of hyperphenylalaninaemia in the population. The detection of BH(4)-responsive PKU patients offers them a less restrictive dietary regimen and an improved quality of life, and may enable near normal life-style in adolescence.