Inborn Errors of Metabolism as Mimickers of Pediatric Neuropsychiatric Disorders: Phenylketonuria as an Example

Phenylalanine hydroxylase (PAH) deficiency, commonly known as phenylketonuria (PKU), is one of the most common inborn errors of amino acid metabolism. It is inherited as an autosomal recessive trait. Prevalance of PKU is approximately 1:10000 in Europe and 1:15000 in the USA but may vary widely in other regions of the world [1]. Due to the high rate of consanguineous marriages (20-25%) [2], diseases with autosomal recessive inheritance are common in Turkey and estimated incidence of persistent hyperphenylalaninemia is one in 4000-4500 live births [3]. Untreated or late-diagnosed PKU may result in central nervous system damage with varying severity, such as intellectual disability, epilepsy, stereotypical movements, autistic features, learning difficulties and attention-deficit hyperactivity disorder. A diet restricted in phenylalanine and supplemented with medical foods containing phenylalanine-free amino acids can prevent severe neurological sequel if started in the first weeks of life, before signs and symptoms become evident [4]. Since early diagnosis with strict longterm treatment provides the best outcomes, newborn screening programs for PKU have been implemented in many countries around the globe, starting with the state of Massachusetts, USA in 1963 after Robert Guthrie invented the simple bacterial inhibition test using dried blood spots [5]. In Turkey, screening of newborns for PKU has been initiated in 1983 as a pilot study and expanded nationwide in 1993 with 50-60% coverage [3]. Screening by the Ministry of Health with coverage up to 95% and more stringent recording protocols has been in effect since 2006 [6].