MUTATIONS IN THE PTERIN-4-ALPHA-CARBINOLAMINE DEHYDRATASE (PCBD) GENECAUSE A BENIGN FORM OF HYPERPHENYLALANINEMIA

Four patients with primapterinuria, postulated to be due to pterin-4 a lpha-carbinolamine dehydratase (PCD) deficiency, were diagnosed by bio chemical and DNA analysis. All four patients presented in the neonatal period with hyperphenylalaninemia, and elevated neopterin and decreas ed biopterin levels in the urine. These symptoms are common to 6-pyruv oyltetrahydropterin synthase deficiency and thus there is a danger of misdiagnosis. In addition, all four patients had elevated urinary excr etion of primapterin (7-biopterin), the only persistent biochemical ab normality. Analysis of fibroblast DNA from the patients identified the following mutations in the PCBD gene: one patient homozygous for the missense mutation E96K and one homozygous for the nonsense mutation Q9 7X, both in exon 4; one compound heterozygote with the mutations E96K and Q97X; and one patient with two different homozygous mutations: E26 X in exon 2 and R87Q in exon 4. In two families, the parents were inve stigated and found to be obligate heterozygotes for particular mutatio ns. One sibling was found to be unaffected. These results further subs tantiate the idea that primapterinuria is associated with mutations in the PCBD gene.