Blood spots on Guthrie cards can be used for inherited tetrahydrobiopterin deficiency screening in hyperphenylalaninaemic infants.

Abstract

SUMMARY We describe a method of screening for dihydropteridine reductase deficiency and dihydrobiopterin synthesis deficiency-the two inherited defects that cause tetrahydrobiopterin deficiency-using blood spots on Guthrie cards. Dihydropteridine reductase deficiency may be identified positively, and a biopterin value of <6-0 [ig/l in the presence of hyperphenylalaninaemia indicates further investigation for dihydrobiopterin synthesis deficiency.Tetrahydropbiopterin deficiency can arise from defective synthesis of dihydrobiopterin,' 2 or from lack of dihydropteridine reductase activity,23 and is a cause of neonatal hyperphenylalaninaemia. Routine screening for phenylketonuria depends upon detection of raised phenylalanine values but does not distinguish hyperphenylalaninaemia arising from tetrahydrobiopterin deficiency from the far more common cause of hyperphenylalaninaemia, phenylalanine hydroxylase deficiency. Tetrahydrobiopterin is the cofactor for the hydroxylation of tyrosine4 and tryptophan5 as well as phenylalanine.Patients with cofactor deficiency develop gross lack of serotonin, dopamine, and noradrenaline. Phenylalanine restriction alone is not the appropriate treatment for these patients who require additional treatment with L-dopa, carbidopa and 5-hydroxytryptophan.

Dihydropteridine reductase activity in eluates from dried blood spots: Automation of an assay for a national screening service

“…In the UK, investigation of patients with HPA for BH 4 deficiency is by a combination of total biopterin and DHPR assay in eluates from dried blood spots on filter paper cards. The manual DHPR assay (Leeming et al, 1984) used initially for this screening service is labour-intensive and unsuited to our workload. Spuriously low activity can be obtained if there is insufficient blood on the card or poor recovery of blood on elution, a problem exacerbated by international variation in absorption and thickness of filter paper card used.…”

Dihydropteridine reductase deficiency in man: From biology to treatment

“…11,46,[81][82][83] Random urine specimens dried on filter paper can also be used, with the advantage that they can be mailed unfrozen. [84][85][86] Samples are oxidized to convert BH 4 , q-BH 2 , and BH 2 to total biopterin, and dihydroneopterin to neopterin. Separation by HPLC then results in pterin profiles characteristic for each form of HPA (Fig.…”

Phenylketonuria in Greece: 12 year's experience

“…Neonatal screening programme revealed that hyperphenylalaninaemia (Hphe) can be caused by absence of any one of the three known essential components of the Phe hydroxylating system (Jervis, 1947;Kaufman, 1978;Scriver & Clow, 1980a, b;Dhond, 1984;Dhond«a/., 1985;Kaufman, 1985;Takahashi ^ra/., 1985;Danks ef a/., 1978;Danks & Cotton, 1980;Curtius et al, 1985;Danks, 1978;Kaufman et al, 1975;Lon$hi etal., 1985;Pfleiderer, 1978;Niederwiesereza/., 1984): (1) inactivation of the Phe hydroxylase (classical PKU); (2) impaired biosynthesis of tetrahydrobioptcrin (BH4); or (3) inactivation of dehydropteridine reductase (DHPR). Identification and treatment of BH4 deficiencies are essential, and have recently become an additional function of screening centers (Firgaira et al, 1979;Niederwieser et al, 1982;Narisawa et al, 1983;Leeming et al, 1984;Matalon, 1984;Sahota et al, 1985).…”