BH4 loading test

BH4 loading test in patients with PAH deficiency. A conventional protocol. 

Tetrahydrobiopterin-responsive PKU Some patients lower their blood phenylalanine in response to a BH4 loading test, particularly if the pure 6R-BH4 diastereoisomer is used. 

Fig. 1.2. Typical results of a BH4 loading test (20 mg/kg body weight) in patients with hyperphenylalaninemia. Tablets of synthetic cofactor (BH4 supplied by Dr. Schircks Laboratories, Jona, Switzerland) were dissolved in 20 ml of water in dim light and administered at least 30 min before a meal. Blood was drawn before, and 4 and 8 hours after BH4 loading. Patients with GTPCH and PTPS deficiencies show a rapid normalization of blood phenylalanine. Simultaneously, there is a transient increase in tyrosine levels 4 hours after the administration of BH4. Basal plasma Phe should be >400 pmol/1...

The first two tests are essential and will allow the differentiation between all variants with BH4 deficiencies. With some limitations (DHPR def.), the BH4 loading test is an additional useful diagnostic tool for the rapid discrimination between classical PKU and biopterin variants. This test is also useful for identifying the recently described BH4-responsive PAH deficiency. For the interpretation and determination of the various disorders based upon loading tests, see Pathological values and differential diagnosis . 

The two forms of BH4 deficiency without hyperphenylalaninemia are detectable only by investigations for neurotransmitter metabolites and pterins in CSF. In DRD, a phenylalanine loading test, a trial with L-Dopa, and enzyme activity measurement in cytokine-stimulated fibroblasts are confirmatory for the diagnosis. SR deficiency can be definitely diagnosed only by an enzyme assay of cultured fibroblasts. 

A combined Phe (lOOmg/kg) and BH4 (20 mg/kg) loading test is sometimes difficult to interpret and is therefore not recommended. 

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