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More girls with phenylketonuria (PKU) enter childbearing ages, and most such women are mentally normal, having been born since newborn screening was initiated in the 1970s and treated from early infancy with a low phenylalanine (Phe) diet. Women with PKU not treated prior to conception can have a pregnancy that results in serious fetal damage1. Maternal PKU as a cause of mental retardation and birth defects is a new phenomenon. There will be an increased need for specific therapies in maternal PKU. Low Phe diet is essential for the treatment of maternal PKU. It should be started before pregnancy and it is necessary to maintain their plasma Phe levels around 5 mg/dl throughout their pregnancy2. However they are usually controlled around 10 mg/dl because of the difficulty of the diet therapy. We made an animal model of maternal PKU by the intravenous injection of Phe to pregnant guinea-pigs, and examined plasma, liver and brain Phe levels in their fetuses after an intravenous administration of 6R-5,6,7,8-tetrahydrobiopterin (R-BH4) to the mothers.

Tetrahydrobiopterin (BH4) synthase deficiency has a high incidence of low birth weight,1 and some of them had a mild mental retardation in spite of their early treatment2. In this study we performed an intravenous loading of 2,4-diamino-6-hydroxypyrimidine (DAHP) with a small amount of BHU, and successfully made a model of fetal BH4 deficiency. We investigated the possibility of the fetal therapy of BH4 deficiency in this model by measurements of phenylalanine(Phe), tyrosine(Tyr), BH4, dopamine and catecholamines.

Tetrahydrobiopterin (BH4) has been used for the therapy of BH4-deficient patients. However, BH4 is poorly absorbed from the intestine. The plasma level of biopterin that was reached after oral administration of BH4 to a BH4-deficient patient was reported to be 1–2% of the levels reached after either intravenous or subcutaneous administration1. This poor absorption from the intestine needs a large amount of BH4 for the oral therapy, leading to high costs.