Phenylalanine and tyrosine metabolism in DNAJC12 deficiency: A comparison between inherited hyperphenylalaninemias and healthy subjects

Abstract DNAJC12 deficiency is a new cause of inherited hyperphenylalaninemia (HPA), besides phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiencies. Differently from other inherited HPAs, no quantitative data on peripheral phenylalanine (Phe) and tyrosine (Tyr) metabolism are currently available in DNAJC12 deficiency. Phe and Tyr metabolism in a patient with DNAJC12 after a simple Phe oral loading test (100 mg/kg) and a combined Phe (100 mg/kg) + BH4 (20 mg/kg) loading test is presented and compared to patients with disorders of BH4 metabolism, PAH deficiency, and healthy controls. Phe and Tyr metabolism in DNAJC12 deficiency is similar to non-PKU HPA. Differently from BH4 deficiency, BH4 administration in DNAJC12 deficiency does not firmly enhance the rate of Phe hydroxylation. A central effect of BH4 treatment in DNAJC12 deficiency cannot be excluded.