Cause:Genetic, autosomal recessive, >250 missense mutations; several different mutations, each with different severity implications (Nejm 1986;314:1276), from mild asx phenylalaninemia to severe PKU
Pathophys:Deficiency of hepatic phenylalanine hydroxylase (converts phenylalanine [PheAla] to tyrosine) causes buildup of PheAla in all body tissues, which in turn leads somehow to mental retardation
Sx:Mental retardation; seizures; behavior problems
Si:Retarded, pale, eczema, blond hair; in adult, psychoses often, even if mentally normal (Nejm 1973;289:395)
Mental retardation in 100% of offspring of affected women unless level kept <10 mg % (Jama 2000;283:756; Nejm 1983;309:1269)
Lab:
Chem:Phenylalanine level >20 mg % is diagnostic; if >2 mg %, repeat it; if >2 mg %, no need for further testing, even if done on 1st day of life and not having eaten yet (Nejm 1981;304:294). Persistent, low (<12 mg %) elevation has no intelligence-impairing effect (Nejm 1971;285:424)
Rx:
Prevent by screening heel blood samples for PheAla once at age 1-3 d (Peds 2001;108:972); find treated PKU girls at age 12 yr to counsel about keeping level <10 during pregnancy to avoid having children with mental retardation (Am J Pub Hlth 1982;72:1386; Nejm 1980;303:1202). Refer all positive screens to tertiary care center.
Diet low in PheAla, commercially prepared; the earlier it is started, the less the retardation; restriction up to age 8 or 10 yr results in higher IQs (Nejm 1986;314:593), but significant financial and cultural barriers to dietary control
Tetrahydrobiopterin po qd may decr PKU levels and allow pts w mild form to relax diet (Nejm 2002;347:2122)