| Because
BH4 deficiencies are a group of diseases which may be detected
due to hyperphenylalaninemia (except
SR deficiency and DRD), but are not routinely identified
through neonatal mass screening, selective screening for
a BH4 deficiency is essential in every newborn with even
slightly elevated phenylalanine levels. Screening for a BH4
deficiency should be done in all newborns with plasma phenylalanine
levels higher than 120 umol/l (2 mg/dl),
as well as in older children with neurological signs and
symptoms.
The following
tests are recommended:
The first two tests are essential and allow to differentiate
between all BH4 defects. With some limitations, the BH4
loading test is an additional, useful diagnostic tool for
the rapid differentiation between classical PKU (non-responder)
and the BH4 variants. In addition this test detects BH4-responsive
PAH-deficient patients (see BIOPKU section). A diagnostic
flow-chart is shown in the Figure.
In order to distinguish between the different variants of
BH4 deficiency, i.e. typical (severe, general) and atypical
(mild, peripheral, partial) forms, quantification of the
neurotransmitter metabolites, 5HIAA and HVA, is essential.
|
