Undiagnosed phenylketonuria in parents of phenylketonuric patients, is it worthwhile to be checked?

• Two cases of mHPA and mPKU diagnosis in Parents of 2 PKU patients are described.
• Disease frequency and the % of mild mutation allow to calculate the risk for a parent to have HPA.
• mHPA or mPKU risk for a parent of a HPA child can vary from 1/68 to 1/708.
• mHPA or mPKU should be detect in parents of HPA patients.

In our phenylketonuria (PKU) cohort of 120 patients, we uncovered a couple of cases of undiagnosed mild phenylketonuria (mPKU)/hyperphenylalaninemia (mHPA) in maternal parents of the PKU cohort. This finding prompted us to evaluate the risk of either mild phenylketonuria or mild hyperphenylalaninemia in the parent population whose children were diagnosed with hyperphenylalaninemia (HPA). Taking into account the phenylalanine hydroxylase (PAH) mutation carrier frequency and the PAH mild mutation rate, we estimated that the prevalence of the parental mPKU/mHPA varied widely, from 1/74 in Turkey to 1/708 in Lithuania. The benefits of the parental detection procedure described here are the prevention of further maternal PKU syndrome, the follow-up of the newly detected patients and the accuracy of the genetic counseling provided to these families. This very simple procedure should be incorporated into neonatal PKU management of the hospitals in countries where a routine systematic neonatal screening is operational.