Here are my GCHI snp's
GCH1 rs10131232 A AA +/+
GCH1 rs11158026 T CT +/-
GCH1 rs2878169 T GT +/-
GCH1 rs3783641 A AT +/-
GCH1 rs3783642 C CC +/+
GCH1 rs4411417 C CT +/-
GCH1 rs7147286 A AG +/-
GCH1 rs752688 T CT +/-
GCH1 rs8017210 A AG +/-
These last two supposedly affect upcycling of BH4 as well but are not GCH1
QDPR rs1031326 T CT +/-
QDPR rs3796809 A AG +/-
Here is other info I read last night I thought was interesting...link is at the end....
In the 1970s, it was discovered that not all HPA was PKU. Some forms of HPA were caused by disorders of synthesis and recycling of the cofactor (tetrahydrobiopterin, or BH4) involved in the Phe hydroxylation reaction. During the 1980s, the human PAH gene was mapped and cloned, and the first pathogenic variants identified. In the 1990s, in vitro expression analysis was being used to study the effects of different PAH alleles on enzyme function and the crystal structure of PAH was elucidated.
HPA is treatable. Affected individuals can lead normal lives. Continuous efforts are made to improve the taste and convenience of the current synthetic dietary supplements [Rohr et al 2001]. Research to improve the current treatment with restrictive phenylalanine diets, supplemented by medical formula, is ongoing (see Management, Therapies Under Investigation).
Differential Diagnosis
Hyperphenylalaninemia (HPA) may also result from the impaired synthesis or recycling of tetrahydrobiopterin (BH4), the cofactor in the phenylalanine, tyrosine, and tryptophan hydroxylation reactions. All of the HPAs caused by BH4 deficiency are inherited in an autosomal recessive manner. They account for approximately 2% of individuals with HPA. BH4 is also involved in catecholamine, serotonin, and nitric oxide biosynthesis (seewww.biopku.org).
Defects in BH4 synthesis result from guanosine triphosphate cyclohydrolase (GTPCH) deficiency caused by mutation of GCH1 or from 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) deficiency caused by mutation of PTS.
Impaired recycling of BH4 is caused by dihydropteridine reductase (DHPR) deficiency caused by mutation of QDPR or by pterin-4 acarbinolamine dehydratase (PCBD) deficiency caused by mutation of PCBD1.
Blau et al [2001] and Scriver & Kaufman [2001] emphasize that all neonates with persistent hyperphenylalaninemia must be screened for the BH4 deficiencies. The following tests are best performed in specialized centers. Prenatal diagnosis is possible for all forms of BH4 deficiencies. The following screening tests are essential:
Analysis of pterins in the urine which will aid in diagnosis of PTPS deficiency, DHPR, and pyruvate carboxylase deficiency (PCD). The pterin profile may be normal for DHPR, and enzyme activity should be measured in erythrocytes or from a dried blood spot.
Other disorders of BH4 metabolism including dopamine-responsive dystonia (DRD) and sepiapterin reductase (SR) deficiency do not have elevations in phenylalanine but abnormalities in pterins can be detected in cerebrospinal fluid (CSF).
Some centers will also perform a loading test with BH4 on babies with a positive newborn screen. This test can rapidly differentiate BH4 deficiencies from PKU.
If screening test results show abnormal pterins, the following confirmatory tests are recommended:
Analysis of folates and neurotransmitter metabolites in CSF. This analysis will help to determine the severity of the BH4 defect [Blau 2006].
Enzyme activity measurements
Molecular genetic testing. Mutation testing for each of the genes involved in BH4 synthesis and recycling is available for confirmatory diagnosis and is useful for prenatal diagnosis. The genotype/phenotype relationships have not been determined and the above biochemical tests are still important for prognostic classification.
The typical (severe) forms of GTPCH, PTPS, and DHPR deficiency have the following variable, but common, findings: intellectual disability, convulsions, disturbance of tone and posture, drowsiness, irritability, abnormal movements, recurrent hyperthermia without infections, hypersalivation, and swallowing difficulties. Microcephaly is common in PTPS and DHPR deficiencies. Plasma phenylalanine concentrations can vary from slightly above normal (>120 μmol/L) to as high as 2500 μmol/L. Mild forms of BH4 deficiency have no clinical signs.
PCD deficiency, sometimes referred to as 'primapterinuria' is associated with benign transient hyperphenylalaninemia.
In principle, BH4 deficiencies are treatable. Treatment requires the normalization of BH4 availability and of blood Phe concentration and restoration of the BH4-dependent hydroxylation of tyrosine and tryptophan. This is achieved by BH4 supplementation along with dietary modification, neurotransmitter precursor replacement therapy, and supplements of folinic acid in DHPR deficiency. The treatment should be initiated early and probably continued for life [Blau et al 2001,Ponzone et al 2006].
More information on the BH4 deficiencies can be found atwww.biopku.org.
http://www.ncbi.nlm.nih.gov/books/NBK1504/
I do think a full PAH test would be great. How was your response to the BH4 btw?