Phenylketonuria (PKU), is an autosomal recessive inborn error of metabolism, in most of cases (about 98%) due to phenylalanine hydroxylase (PAH) deficiency; the other (2%) of cases arise from disorders in tetrahydrobiopterin (BH4) synthesis or regeneration. BH4-responsive hyperphenylalaninaemia (HPA) is a recently described variant of PAH deficiency caused by specific mutations in the PAH gene. BH4 loading test or a combined Phe/BH4 loading test is included in the work-up of HPA. As defined by literature, patients with mild hyperphenylalaninemia (MHP) require a combined Phe/BH4 loading test, for which the possibility of plasma Phe's spontaneous elimination has to be considered. It has intact been reported that after a single 100 mg/kg Phe load (without BH4) in MHP patients plasma Phe levels return spontaneously to pre-load values within 24-48h. In Europe, BH4-loading test is mostly performed during neonatal period, because of high Phe levels and its practice to do it. This test is considered positive when initial plasma Phe concentrations decrease by at least 30% in the first 8 hrs and subsequently. It is known that serum Phe concentrations decrease after Bh4 administration in BH4 deficiency, but not in PAH deficiency. We report three cases of MHP patients diagnosed by neonatal screening. Their basal plasma Phe levels were 340.6, 330.1 and 328 micromol/l, respectively. Because their Phe levels were near to the cutoff (360 micromol/L) we then decided to do only BH4 loading dose (20 mg/kg at h 0 and h 24), without Phe loading test. All patients reported 53.7%, 67.1% and 34.7% plasma Phe levels decrease after 8h, respectively. Molecular analysis result was (first patient: IVS12+1g>a, A300S; second patient: R297H, P281L and the third: R261Q, P366H). No BH4 or DHPR deficiencies were reported; pterins levels were normal. As our patients were found to be BH4 responsive without performing Phe loading test and since their basal Phe levels were below the Phe cutoff 360 micromol/l), we can suggest that Phe loading test is not necessary for these kind of MHP patients. Our result needs more studies and number of cases to be further confirmed, but it can establish the importance of single BH4 loading test incorporation in the management of neonates screened for MHP.

Is phenylalanine (Phe) loading test still necessary for hyperphenylalaninemia patient with basal plasma level < 360 micromol/l? / R. Selmi, E. Salvatici, V. Rovelli, S. Paci, E. Riva. ((Intervento presentato al convegno International Conference on Tetrahydrobiopterin, Phenylketonuria, Monoamine Neurotransmitters and Nitric Oxide Synthase tenutosi a St Moritz, nel 2013.

Is phenylalanine (Phe) loading test still necessary for hyperphenylalaninemia patient with basal plasma level < 360 micromol/l?

R. Selmi
Primo
;
E. Salvatici
Secondo
;
S. Paci
Penultimo
;
E. Riva
Ultimo
2013

Abstract

Phenylketonuria (PKU), is an autosomal recessive inborn error of metabolism, in most of cases (about 98%) due to phenylalanine hydroxylase (PAH) deficiency; the other (2%) of cases arise from disorders in tetrahydrobiopterin (BH4) synthesis or regeneration. BH4-responsive hyperphenylalaninaemia (HPA) is a recently described variant of PAH deficiency caused by specific mutations in the PAH gene. BH4 loading test or a combined Phe/BH4 loading test is included in the work-up of HPA. As defined by literature, patients with mild hyperphenylalaninemia (MHP) require a combined Phe/BH4 loading test, for which the possibility of plasma Phe's spontaneous elimination has to be considered. It has intact been reported that after a single 100 mg/kg Phe load (without BH4) in MHP patients plasma Phe levels return spontaneously to pre-load values within 24-48h. In Europe, BH4-loading test is mostly performed during neonatal period, because of high Phe levels and its practice to do it. This test is considered positive when initial plasma Phe concentrations decrease by at least 30% in the first 8 hrs and subsequently. It is known that serum Phe concentrations decrease after Bh4 administration in BH4 deficiency, but not in PAH deficiency. We report three cases of MHP patients diagnosed by neonatal screening. Their basal plasma Phe levels were 340.6, 330.1 and 328 micromol/l, respectively. Because their Phe levels were near to the cutoff (360 micromol/L) we then decided to do only BH4 loading dose (20 mg/kg at h 0 and h 24), without Phe loading test. All patients reported 53.7%, 67.1% and 34.7% plasma Phe levels decrease after 8h, respectively. Molecular analysis result was (first patient: IVS12+1g>a, A300S; second patient: R297H, P281L and the third: R261Q, P366H). No BH4 or DHPR deficiencies were reported; pterins levels were normal. As our patients were found to be BH4 responsive without performing Phe loading test and since their basal Phe levels were below the Phe cutoff 360 micromol/l), we can suggest that Phe loading test is not necessary for these kind of MHP patients. Our result needs more studies and number of cases to be further confirmed, but it can establish the importance of single BH4 loading test incorporation in the management of neonates screened for MHP.
mar-2013
Settore MED/38 - Pediatria Generale e Specialistica
Is phenylalanine (Phe) loading test still necessary for hyperphenylalaninemia patient with basal plasma level < 360 micromol/l? / R. Selmi, E. Salvatici, V. Rovelli, S. Paci, E. Riva. ((Intervento presentato al convegno International Conference on Tetrahydrobiopterin, Phenylketonuria, Monoamine Neurotransmitters and Nitric Oxide Synthase tenutosi a St Moritz, nel 2013.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/223448
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