Phenylketonuria (PKU)  is the most frequent inborn error of the amino acid metabolism (prevalence about 1:10,000 newborns). These autosomal-recessive inherited variants lead to deficiency in the PAH enzyme which hydroxylates phenylalanine to tyrosine, with the help of a cofactor (tetrahydrobiopterin; BH4), molecular oxygen, and non-heme iron. The metabolic picture is highly heterogenous as it depends on the degree of residual PAH activity and blood phenylalanine (Phe) concentrations. Untreated PKU generally results in global developmental delay or severe irreversible intellectual disability, as well as growth failure, hypopigmentation, motor deficits, ataxia, and seizures. The population of PKU-affected individuals is heterogeneous in terms of treatment history and diet compliance. Early diagnosis and treatment with a low-Phe diet has enabled an almost normal life for the majority of PKU subject. Pharmacological treatment with BH4 (sapropterin) and enzyme substitution therapy with Phe ammonia lyase (PAL) provide alternative treatment options for some PKU subjects. Several gene therapy trials are on the way.
The book includes the latest advancements in the pathophysiology of PKU, which is still not fully understood, as well as its management with new therapeutic options.

Nenad Blau, is a Senior Consultant in Biochemical Genetics at the University Children’s Hospital of Zürich, Switzerland, and Professor emeritus in Clinical Biochemistry at the University of Zürich. He served in the same function at the Children’s Hospital in Heidelberg, Germany from 2011-2019. He was the Head of the Laboratory for Tetrahydrobiopterin and Neurotransmitter Diseases at the University Children’s Hospital in Zürich, Switzerland, where his research group discovered several inborn errors of metabolism, including GTPCH, PCD and SR deficiencies. He established and curated the phenylalanine hydroxylase (PAH) locus-specific database, BIOPKU database of phenylketonuria (PKU) genotypes, database of tetrahydrobiopterin (BH4) deficiencies and the PND database of variants causing pediatric neurotransmitter disorders (https://www.biopku.org). With colleagues from Vancouver (BC, Canada), he developed the IEM base, an online knowledgebase and diagnostic tool for inborn errors of metabolism (https://www.iembase.org).
His current research focuses on epidemiology, population genetics, genotype-phenotype correlation, and genotypic phenotype prediction in PKU and other inherited metabolic diseases. Prof. Blau is an honorary member of the Italian Society for Pediatrics and of the German Society for Inherited Metabolic Disorders. In 2001, he received the Horst¬ Bickel-Award, in 2005 the Gowland Hopkins Award and in 2011 the Asbjørn Følling Award for his research in the field of tetrahydrobiopterin and PKU. Prof. Blau is author of more than 450 research publications and 12 books, including the standard textbooks ‘Physician's Guide to the Diagnosis, Treatment and Follow-up of Inherited Metabolic Diseases’ and ‘Laboratory Guide to the Methods in Biochemical Genetics’. Currently he serves as Deputy Editor-in-Chief for the journal Molecular Genetics and Metabolism.