Nenad Blau – The PKU Book

Автор: Nenad Blau
Название: The PKU Book
Формат: PDF
Тема: Медицина
Количество страниц: 528
Качество: Компьютерное, издательское

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.