PCD deficiency

A Fig. 6.1.7a- HPLC of pterins using a column-switching system a standard mixture b control urine c urine guanosine triphosphate cyclohydrolase I (GTPCH) deficiency d urine 6-pyru-voyl-tetrahydropterin synthase (PTPS) deficiency e urine pterin-4a-carbinolamine dehydratase (PCD) deficiency f urine dihydropteridine reductase (DHPR) deficiency g urine phenylketonuria 4-8 h after tetrahydrobiopterin (BH4) administration h-k see next page... 

PCD deficient patients excrete 7-biopterin (137), called primaterin, in their urine [152-154], which had not been observed in normal mammals. The mechanism of the 7-substituted pterin synthesis from 6-substitute has been proposed [155,156] (Scheme 33). When 95 is rapidly dehydrated to 45 via PCD, the dihydroxypropyl side chain of 95 is retained at its 6-position. However, in the absence of PCD activity, the rate of conversion of unstable 95 is slow. Therefore, its pyrazine ring is opened to give 98, and recyclization of 98 to the 7-substituted pterin derivative proceeds via spiro intermediate 138 [89,156]. 

Pterin carbinolamine-4fi[- dehydratase (PCD) deficiency (Primapterinuria) Without hyperphenylalaninemia liver, kidney, intestine 10q22 264070... 

BH4 deficiency can be caused by mutations in genes encoding the enzymes involved in its biosynthesis (GTPCH, PTPS, and SR) or regeneration (PCD/DCoH and DHPR). BH4 deficiency due to autosomal recessive mutations in BH4-metabo-lizing enzymes (except SR) has been described as a cause of hyperphenylalaninemia (HPA) [6]. Biochemical, clinical, and DNA data of patients with BH4 deficiencies are tabulated in the BIODEF and BIOMDB databases and are available on the Internet (www.bh4.org) [7]. Depending on the enzyme defect and the mode of inheritance,... 

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