Introduction: PKU is a metabolic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene. Icelandic neonatal screening for PKU started in 1972. The mutation causes a varible dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Accumulation of Phe causes mental retardation and seizures. Current therapy focuses on Phe-restrictive diet and newer methods like BH4 in large doses. The primary aim was to collect data about PKU in Iceland and evaluate therapy and screening. Additional focus was on BH4 therapy.

Materials and methods: Information was gathered from Landspitali medical charts retrospectively. Serum-Phe (S-Phe) measurements, age at initiation of therapy, PAH mutation types and information on current therapy was collected. Results from BH4 loading tests were collected.

Results: 27 patients have been diagnosed with PKU in Iceland since 1947. Incidence 1972-2008 is 1/8400 living births. Classic PKU is the most common presentation in Iceland. Patients diagnosed after screening started have normal intelligence. Age at initiation of therapy and S-Phe average values lower with time. 12 PAH mutation types have been found in Iceland. A novel Icelandic mutation, Y377fsdelT, did not respond to BH4 loading test. Two patients responded to a BH4 loading test and four other patients are likely to respond to BH4 loading test.

Conclusion: PKU incidence in Iceland is slightly higher than in neighboring countries. Therapy compliance is adequate and international consensuses regarding therapy are met. PKU patients in Iceland are generally in good health. Screening is efficient and save. BH4 therapy is a an optional alternative therapy in Iceland.

Key words: Phenylketonuria (PKU), incidence, screening, therapy, phenylalanine hydroxylase (PAH), tetrahydrobiopterin (BH4), Serum-Phe (S-Phe).

Correspondence: Atli Dagbjartsson, atlid@landspitali.is

Table I: The results of PKU-therapy before and after screening started. Age at the beginning of therapy and patient health is taken into consideration.

Table II: Icelandic PKU patients grouped according to S-Phe level without therapy, klassísk (classic) PKU being most severe.

Table III: BH4-loading test results from four PKU patients. S-Phe changes are observed 24 hours after BH4-loading dose. If the decrease in S-Phe is >30% at eight hours, or >50% 24 hours later, the patient responds to the test.

Table IV: Types of mutations and number of alleles in the PAH-gene of all 27 Icelandic PKU patients.

Picture 1: Age at the beginning of therapy. Patients are sorted according to age, the oldest to the far left. The best line is shown in the picture.

Picture 2: Median and mean values of S-Phe the first 42 months for PKU patients born 1989-2002. Patients are sorted according to age, the oldest to the far left. The best line is shown in the picture.