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California Newborn Screening Program

Cofactor Variants

Cofactor variants involve enzyme deficiencies in the cofactor pathway. This disorder makes up approximately 2% of PKU cases in California; it is not the phenylalanine-hydroxylase deficiency of classical PKU. Tetrahydrobiopterin (BH4) is also a cofactor in neurotransmitter pathways. The enzymes dihydropteridine reductase (DHPR), dihydrobiopterin synthase (DHBS), and guanosine triphosphate-cyclohydrolase (GTPCH) are required to produce the cofactor BH4. A deficiency in any one of these enzymes can result in defective serotonin and catecholamine production. These patients have progressive neurological damage with seizures and deterioration, which become noticeable between two and twenty months of age despite a low-phe diet.

Diagnosis is made by testing a child whose serum phe level repeats positive before a low-phe diet is established and while the plasma phe levels are still high. Due to the very serious nature of these cofactor deficiencies, each newborn with repeatedly elevated phe levels should have biopterin testing to rule out this possibility. (This testing is done at the Genetics Disease Screening Laboratory, and it is part of the Newborn Screening Program, provided at no extra charge to the family.)


Last modified on: 12/10/2012 9:07 AM