Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by a defect in the hepatic enzyme phenylalanine hydroxylase (PAH) characterized by elevated levels of blood phenylalanine (Phe) leading to severely impaired brain development. In addition to poor neurological outcomes, untreated PKU can lead to microcephaly, tremor of hands, epilepsy, spastic paraparesis, behavioral problems, and schizophrenia. Early diagnosis and inception of a Phe-restricted diet after the newborn period prevents mental retardation and other neurological symptoms in PKU patients. With PKU, various mutations of the PAH gene have been identified along with their severity based on their enzyme activity. One of the main motivations for measuring brain Phe levels is that new drugs may limit/reduce the transport of Phe into the brain. Thus, plasma Phe levels might be insufficient surrogate markers for brain Phe levels. However, the detection and quantitation of brain Phe with in vivo MR spectroscopy is uniquely challenging due to its low concentration and the position of Phe resonance (7.36 ppm) in a part of the spectrum that is generally not look at. Thus for measuring Phe accurately, a high level of expertise for acquiring high-quality data and advanced processing methods are required. It is for that reason, albeit phenylketonuria is a comparably frequently encountered metabolic disease that only few groups have attempted to explore the value of MRS in PKU.
KeywordsIntelligence Quotient Large Neutral Amino Acid Blood Phenylalanine Phenylpyruvic Acid Autosomal Recessive Genetic Disorder
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