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Phenylketonuria

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MR Spectroscopy of Pediatric Brain Disorders

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Abstract

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.

Dr. Koch was a pioneer in providing medical services to the disabled and led the efforts that resulted in routine newborn screening for PKU and other inborn errors. We are grateful for his willingness to put together a chapter about MRS and PKU. Dr. Koch passed away on September 24th, 2011, at the age of 89.

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Authors and Affiliations

  1. Childrens Hospital Los Angeles, Los Angeles, CA, 90027, USA

    Arabhi Nagasunder M.S.

  2. Rudi Schulte Research Institute, Santa Barbara, CA, USA

    Arabhi Nagasunder M.S.

  3. USC Keck School of Medicine, Los Angeles, CA, USA

    Richard Koch M.D. (Professor Emeritus)

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  1. Arabhi Nagasunder M.S.
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  2. Richard Koch M.D.
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Correspondence to Arabhi Nagasunder M.S. .

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Editors and Affiliations

  1. Keck School of Medicine, Dept. Radiology, University of Southern California, Zonal Avenue 1975, Los Angeles, 90089-9034, California, USA

    Stefan Blüml

  2. , Dept. of Pediatric Radiology, Children's Hospital of Pittsburg of UPMC, Penn Avenue 4401, Pittsburgh, 15224, Pennsylvania, USA

    Ashok Panigrahy

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Nagasunder, A., Koch, R. (2013). Phenylketonuria. In: Blüml, S., Panigrahy, A. (eds) MR Spectroscopy of Pediatric Brain Disorders. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5864-8_12

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  • DOI: https://doi.org/10.1007/978-1-4419-5864-8_12

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  • Print ISBN: 978-1-4419-5863-1

  • Online ISBN: 978-1-4419-5864-8

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