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GTPCH		GFRP		PTPS		SR		PCD		DHPR

Phenylalanine loading test in Dopa-responsive dystonia (DRD due to GTPCH deficiency) and other forms of tetrahydrobiopterin deficiency without hyperphenylalaninemia (SR deficiency)

Dosage

100 mg/kg (oral load)

Sample collection

1 ml plasma (Heparin or EDTA) 0, 1, 2, and 4 hrs after administration of Phe, keep frozen at -20°C

Measurements

Phenylalanine, tyrosine, neopterin, and biopterin

Interpretation

Phenylalanine levels peak at 2 hrs and are markedly elevated at 4 and 6 hrs compared to controls. Tyrosine levels do not increase at all.

The slower clearance rate of phenylalanine from the plasma and inadequate production of tyrosine indicate a defect in liver PAH activity in patients with DRD.

Similar Plasma Phe/Tyr profiles can be expected in patients with other forms of BH4 deficiency.

Figure 5 - Preload : Phe, Phe/Tyr, and biopterin

Reference

• Hyland K, Fryburg JS, Wilson WG, Bebin EM, Arnold LA, Gunasekera RS, Jacobson RD, Rostruffner E, Trugman JM. Oral phenylalanine loading in Dopa-responsive dystonia - a possible diagnostic test. Neurology 1997 48, 1290-1297.
   
• Blau N, Bonafé L, Thöny B. Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: Diagnosis and genetics of Dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab 2001:in press.