Tetrahydrobiopterin loading test in differential diagnosis among hyperphenylalaninemia patients

Objective To perform tetrahydrobiopterin (BH4) loading test and to further understand its usefulness in differential diagnosis among hyperphenylalaninemia(HPA) patients. Methods BH4 loading test was carried out in 73 HPA patients, including the positive cases unveiled by neonatal screening and the clinically suspected cases. These patients, 47 males and 26 females, were at a mean age of 1.93 months. BH4 (20 mg/kg) loading test was performed in all patients, and a combined phenylalanine (Phe)(100 mg/kg) and BH4 loading test was performed among the patient who had a basic blood Phe concentration less than 600 μmol/L. The urine pterine profile analysis and the dihydropteridine reductase activity in dry blood filter spot were tested simultaneously. Results During BH4 loading test or combined Phe and BH4 loading test, the patients with classic phenylketonuria showed no response to BH4, the patients with moderate HPA caused by Phe hydroxylase deficiency decreased 32.8% of blood Phe level and the patients with BH4 deficiency showed a prompt reduction in blood Phe level and it decreased to normal level at 4 h and lasted until 24 h. Twenty-two cases were diagnosed as classic phenylketonuria, 39 were moderate phenylketonuria and 12 were BH4 deficiency. Conclusion Hyperphenylalaninemia may be caused by deficiency of Phe hydroxylase or by deficiency of co-factor BH4. Early diagnosis is important. BH4 loading test is a safe and fast test in vivo. It is sensitive, easy-to-do, and is highly useful in differential diagnosis for suspected cases of HPA.