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Metabolic Disorders

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MR Spectroscopy of Pediatric Brain Disorders

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Abstract

Magnetic resonance spectroscopy (MRS) provides a powerful tool in narrowing the differential diagnosis in pediatric brain disorders. The foremost utility of MRS should be the recognition of metabolic disorders, especially within the context of early detection, as the specificity of imaging is limited until macroscopic structural changes have occurred. Unfortunately, the literature provides only a limited number of case reports and small patient series employing MRS in the diagnosis and monitoring of metabolic diseases. This is likely because many metabolic disorders are rare, and tend to present during childhood as well as the inherent limitations of MRS, which include the ability to only primarily detect cellular events (neuronal dysfunction, lactic academia, abnormal myelination, gliosis, etc.) and low signal to noise ratio (SNR). This chapter will describe diseases such as lysosomal storage diseases, mitochondrial disorders, amino acidurias, organic acidurias, urea cycle defects, creatine disorders, and other miscellaneous metabolic disorders.

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References

  1. Confort-Gouny S, Chabrol B, Vion-Dury J, Mancini J, Cozzone PJ. MRI and localized proton MRS in early infantile form of neuronal ceroid-lipofuscinosis. Pediatr Neurol. 1993;9(1):57–60.

    Article  PubMed  CAS  Google Scholar 

  2. Brockmann K, Pouwels PJ, Christen HJ, Frahm J, Hanefeld F. Localized proton magnetic resonance spectroscopy of cerebral metabolic disturbances in children with neuronal ceroid lipofuscinosis. Neuropediatrics. 1996;27(5):242–8.

    Article  PubMed  CAS  Google Scholar 

  3. Seitz D, Grodd W, Schwab A, Seeger U, Klose U, Nagele T. MR imaging and localized proton MR spectroscopy in late infantile neuronal ceroid lipofuscinosis. AJNR Am J Neuroradiol. 1998;19(7):1373–7.

    PubMed  CAS  Google Scholar 

  4. Vanhanen SL, Puranen J, Autti T, et al. Neuroradiological findings (MRS, MRI, SPECT) in infantile neuronal ceroid-lipofuscinosis (infantile CLN1) at different stages of the disease. Neuropediatrics. 2004;35(1):27–35.

    Article  PubMed  Google Scholar 

  5. Sitter B, Autti T, Tyynela J, et al. High-resolution magic angle spinning and 1 H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3. J Neurosci Res. 2004;77(5):762–9.

    Article  PubMed  CAS  Google Scholar 

  6. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5:16.

    Article  PubMed  Google Scholar 

  7. Tedeschi G, Bonavita S, Barton NW, et al. Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease. J Neurol Neurosurg Psychiatry. 1998;65(1):72–9.

    Article  PubMed  CAS  Google Scholar 

  8. Sylvain M, Arnold DL, Scriver CR, Schreiber R, Shevell MI. Magnetic resonance spectroscopy in Niemann-Pick disease type C: correlation with diagnosis and clinical response to cholestyramine and lovastatin. Pediatr Neurol. 1994;10(3):228–32.

    Article  PubMed  CAS  Google Scholar 

  9. Galanaud D, Tourbah A, Lehericy S, et al. 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. 2009;96(2):55–8.

    Article  PubMed  CAS  Google Scholar 

  10. Varho T, Komu M, Sonninen P, et al. A new metabolite contributing to N-acetyl signal in 1 H MRS of the brain in Salla disease. Neurology. 1999;52(8):1668–72.

    Article  PubMed  CAS  Google Scholar 

  11. Suhonen-Polvi H, Varho T, Metsahonkala L, et al. Increased brain glucose utilization in Salla disease (free sialic acid storage disorder). J Nucl Med. 1999;40(1):12–8.

    PubMed  CAS  Google Scholar 

  12. Kaback M, Lim-Steele J, Dabholkar D, Brown D, Levy N, Zeiger K. Tay-Sachs disease—carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA. 1993;270(19):2307–15.

    Article  PubMed  CAS  Google Scholar 

  13. Kaback MM. Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. Eur J Pediatr. 2000;159 Suppl 3:S192–195.

    Article  PubMed  CAS  Google Scholar 

  14. Aydin K, Bakir B, Tatli B, Terzibasioglu E, Ozmen M. Proton MR spectroscopy in three children with Tay-Sachs disease. Pediatr Radiol. 2005;35(11):1081–5.

    Article  PubMed  Google Scholar 

  15. Imamura A, Miyajima H, Ito R, Orii KO. Serial MR imaging and 1 H-MR spectroscopy in monozygotic twins with Tay-Sachs disease. Neuropediatrics. 2008;39(5):259–63.

    Article  PubMed  CAS  Google Scholar 

  16. Felderhoff-Mueser U, Sperner J, Konstanzcak P, Navon R, Weschke B. 31Phosphorus magnetic resonance spectroscopy in late-onset Tay-Sachs disease. J Child Neurol. 2001;16(5):377–80.

    Article  PubMed  CAS  Google Scholar 

  17. Wilken B, Dechent P, Hanefeld F, Frahm J. Proton MRS of a child with Sandhoff disease reveals elevated brain hexosamine. Eur J Paediatr Neurol. 2008;12(1):56–60.

    Article  PubMed  CAS  Google Scholar 

  18. Lowe JP, Stuckey DJ, Awan FR, et al. MRS reveals additional hexose N-acetyl resonances in the brain of a mouse model for Sandhoff disease. NMR Biomed. 2005;18(8):517–26.

    Article  PubMed  CAS  Google Scholar 

  19. Miyanomae Y, Ochi M, Yoshioka H, et al. Cerebral MRI and spectroscopy in Sjogren-Larsson syndrome: case report. Neuroradiology. 1995;37(3):225–8.

    Article  PubMed  CAS  Google Scholar 

  20. Mano T, Ono J, Kaminaga T, et al. Proton MR spectroscopy of Sjogren-Larsson’s syndrome. AJNR Am J Neuroradiol. 1999;20(9):1671–3.

    PubMed  CAS  Google Scholar 

  21. Willemsen MA, Van Der Graaf M, Van Der Knaap MS, et al. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004;25(4):649–57.

    PubMed  Google Scholar 

  22. Willemsen MA, Lutt MA, Steijlen PM, et al. Clinical and biochemical effects of zileuton in patients with the Sjogren-Larsson syndrome. Eur J Pediatr. 2001;160(12):711–7.

    PubMed  CAS  Google Scholar 

  23. Willemsen MA, Ijlst L, Steijlen PM, et al. Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjogren-Larsson syndrome. Brain. 2001;124(Pt 7):1426–37.

    Article  PubMed  CAS  Google Scholar 

  24. Willemsen MA, Rotteveel JJ, Steijlen PM, Heerschap A, Mayatepek E. 5-Lipoxygenase inhibition: a new treatment strategy for Sjogren-Larsson syndrome. Neuropediatrics. 2000;31(1):1–3.

    Article  PubMed  CAS  Google Scholar 

  25. Nakayama M, Tavora DG, Alvim TC, Araujo AC, Gama RL. MRI and 1H-MRS findings of three patients with Sjogren-Larsson syndrome. Arq Neuropsiquiatr. 2006;64(2B):398–401.

    Article  PubMed  Google Scholar 

  26. Lossos A, Khoury M, Rizzo WB, et al. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006;63(2):278–80.

    Article  PubMed  Google Scholar 

  27. Pirgon O, Aydin K, Atabek ME. Proton magnetic resonance spectroscopy findings and clinical effects of montelukast sodium in a case with Sjogren-Larsson syndrome. J Child Neurol. 2006;21(12):1092–5.

    Article  PubMed  Google Scholar 

  28. Kaminaga T, Mano T, Ono J, Kusuoka H, Nakamura H, Nishimura T. Proton magnetic resonance spectroscopy of Sjogren-Larsson syndrome heterozygotes. Magn Reson Med. 2001;45(6):1112–5.

    Article  PubMed  CAS  Google Scholar 

  29. DiMauro S. Mitochondrial DNA medicine. Biosci Rep. 2007;27(1–3):5–9.

    Article  PubMed  CAS  Google Scholar 

  30. Pavlakis SG, Kingsley PB, Kaplan GP, Stacpoole PW, O’Shea M, Lustbader D. Magnetic resonance spectroscopy: use in monitoring MELAS treatment. Arch Neurol. 1998;55(6):849–52.

    Article  PubMed  CAS  Google Scholar 

  31. Wilichowski E, Pouwels PJ, Frahm J, Hanefeld F. Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS. Neuropediatrics. 1999;30(5):256–63.

    Article  PubMed  CAS  Google Scholar 

  32. Castillo M, Kwock L, Green C. MELAS syndrome: imaging and proton MR spectroscopic findings. AJNR Am J Neuroradiol. 1995;16(2):233–9.

    PubMed  CAS  Google Scholar 

  33. Dinopoulos A, Cecil KM, Schapiro MB, et al. Brain MRI and proton MRS findings in infants and children with respiratory chain defects. Neuropediatrics. 2005;36(5):290–301.

    Article  PubMed  CAS  Google Scholar 

  34. Bianchi MC, Sgandurra G, Tosetti M, Battini R, Cioni G. Brain magnetic resonance in the diagnostic evaluation of mitochondrial encephalopathies. Biosci Rep. 2007;27(1–3):69–85.

    Article  PubMed  CAS  Google Scholar 

  35. Lin DD, Crawford TO, Barker PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol. 2003;24(1):33–41.

    PubMed  Google Scholar 

  36. Barkovich AJ, Good WV, Koch TK, Berg BO. Mitochondrial disorders: analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol. 1993;14(5):1119–37.

    PubMed  CAS  Google Scholar 

  37. Boddaert N, Romano S, Funalot B, et al. 1 H MRS spectroscopy evidence of cerebellar high lactate in mitochondrial respiratory chain deficiency. Mol Genet Metab. 2008;93(1):85–8.

    Article  PubMed  CAS  Google Scholar 

  38. Filosto M, Tomelleri G, Tonin P, et al. Neuropathology of mitochondrial diseases. Biosci Rep. 2007;27(1–3):23–30.

    Article  PubMed  CAS  Google Scholar 

  39. Brockmann K, Bjornstad A, Dechent P, et al. Succinate in dystrophic white matter: a proton magnetic resonance spectroscopy finding characteristic for complex II deficiency. Ann Neurol. 2002;52(1):38–46.

    Article  PubMed  CAS  Google Scholar 

  40. Heindel W, Kugel H, Roth B. Noninvasive detection of increased glycine content by proton MR spectroscopy in the brains of two infants with nonketotic hyperglycinemia. AJNR Am J Neuroradiol. 1993;14(3):629–35.

    PubMed  CAS  Google Scholar 

  41. Gabis L, Parton P, Roche P, Lenn N, Tudorica A, Huang W. In vivo 1 H magnetic resonance spectroscopic measurement of brain glycine levels in nonketotic hyperglycinemia. J Neuroimaging. 2001;11(2):209–11.

    Article  PubMed  CAS  Google Scholar 

  42. Huisman TA, Thiel T, Steinmann B, Zeilinger G, Martin E. Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic hyperglycinemia: in vivo-in vitro (ex vivo) correlation. Eur Radiol. 2002;12(4):858–61.

    Article  PubMed  CAS  Google Scholar 

  43. Viola A, Chabrol B, Nicoli F, Confort-Gouny S, Viout P, Cozzone PJ. Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia. Pediatr Res. 2002;52(2):292–300.

    Article  PubMed  CAS  Google Scholar 

  44. Tekgul H, Serdaroglu G, Karapinar B, et al. Vigabatrin caused rapidly progressive deterioration in two cases with early myoclonic encephalopathy associated with nonketotic hyperglycinemia. J Child Neurol. 2006;21(1):82–4.

    Article  PubMed  Google Scholar 

  45. Kugel H, Roth B, Pillekamp F, et al. Proton spectroscopic metabolite signal relaxation times in preterm infants: a prerequisite for quantitative spectroscopy in infant brain. J Magn Reson Imaging. 2003;17(6):634–40.

    Article  PubMed  Google Scholar 

  46. Kreis R, Ernst T, Ross BD. Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med. 1993; 30(4):424–37.

    Article  PubMed  CAS  Google Scholar 

  47. Prescot AP, de B Frederick B, Wang L, et al. In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T. Magn Reson Med. 2006;55(3):681–6.

    Article  PubMed  CAS  Google Scholar 

  48. Manley BJ, Sokol J, Cheong JL. Intracerebral blood and MRS in neonatal nonketotic hyperglycinemia. Pediatr Neurol. 2010; 42(3):219–22.

    Article  PubMed  Google Scholar 

  49. Hoffmann GF, Athanassopoulos S, Burlina AB, et al. Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics. 1996;27(3):115–23.

    Article  PubMed  CAS  Google Scholar 

  50. Moller HE, Koch HG, Weglage J, Freudenberg F, Ullrich K. Investigation of the cerebral energy status in patients with glutaric aciduria type I by 31P magnetic resonance spectroscopy. Neuropediatrics. 2003;34(2):57–60.

    Article  PubMed  CAS  Google Scholar 

  51. Elster AW. Glutaric aciduria type I: value of diffusion-weighted magnetic resonance imaging for diagnosing acute striatal necrosis. J Comput Assist Tomogr. 2004;28(1):98–100.

    Article  PubMed  Google Scholar 

  52. Santos CC, Roach ES. Glutaric aciduria type I: a neuroimaging diagnosis? J Child Neurol. 2005;20(7):588–90.

    PubMed  Google Scholar 

  53. Kurul S, Cakmakci H, Dirik E. Glutaric aciduria type 1: proton magnetic resonance spectroscopy findings. Pediatr Neurol. 2004;31(3):228–31.

    Article  PubMed  Google Scholar 

  54. Oguz KK, Ozturk A, Cila A. Diffusion-weighted MR imaging and MR spectroscopy in glutaric aciduria type 1. Neuroradiology. 2005;47(3):229–34.

    Article  PubMed  CAS  Google Scholar 

  55. Sijens PE, Smit GP, Meiners LC, Oudkerk M, van Spronsen FJ. Cerebral 1 H MR spectroscopy revealing white matter NAA decreases in glutaric aciduria type I. Mol Genet Metab. 2006;88(3):285–9.

    Article  PubMed  CAS  Google Scholar 

  56. Firat AK, Karakas HM, Yakinci C. Magnetic resonance spectroscopic characteristics of glutaric aciduria type II. Dev Med Child Neurol. 2006;48(10):847–50.

    Article  PubMed  Google Scholar 

  57. Rzem R, Veiga-da-Cunha M, Noel G, et al. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc Natl Acad Sci USA. 2004;101(48):16849–54.

    Article  PubMed  CAS  Google Scholar 

  58. Topcu M, Jobard F, Halliez S, et al. L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. Hum Mol Genet. 2004;13(22):2803–11.

    Article  PubMed  CAS  Google Scholar 

  59. D’Incerti L, Farina L, Moroni I, Uziel G, Savoiardo M. L-2-Hydroxyglutaric aciduria: MRI in seven cases. Neuroradiology. 1998;40(11):727–33.

    Article  PubMed  Google Scholar 

  60. Seijo-Martinez M, Navarro C, Castro del Rio M, et al. L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings. Arch Neurol. 2005;62(4):666–70.

    Article  PubMed  Google Scholar 

  61. Steenweg ME, Salomons GS, Yapici Z, et al. L-2-Hydroxyglutaric aciduria: pattern of MR imaging abnormalities in 56 patients. Radiology. 2009;251(3):856–65.

    Article  PubMed  Google Scholar 

  62. Topcu M, Aydin OF, Yalcinkaya C, et al. L-2-hydroxyglutaric aciduria: a report of 29 patients. Turk J Pediatr. 2005;47(1):1–7.

    PubMed  Google Scholar 

  63. Hanefeld F, Kruse B, Bruhn H, Frahm J. In vivo proton magnetic resonance spectroscopy of the brain in a patient with L-2-hydroxyglutaric acidemia. Pediatr Res. 1994;35(5):614–6.

    Article  PubMed  CAS  Google Scholar 

  64. Sener RN. L-2 hydroxyglutaric aciduria: proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging findings. J Comput Assist Tomogr. 2003;27(1):38–43.

    Article  PubMed  Google Scholar 

  65. Aydin K, Ozmen M, Tatli B, Sencer S. Single-voxel MR spectroscopy and diffusion-weighted MRI in two patients with l-2-hydroxyglutaric aciduria. Pediatr Radiol. 2003;33(12):872–6.

    Article  PubMed  Google Scholar 

  66. Felber SR, Sperl W, Chemelli A, Murr C, Wendel U. Maple syrup urine disease: metabolic decompensation monitored by proton magnetic resonance imaging and spectroscopy. Ann Neurol. 1993;33(4):396–401.

    Article  PubMed  CAS  Google Scholar 

  67. Heindel W, Kugel H, Wendel U, Roth B, Benz-Bohm G. Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease. Pediatr Radiol. 1995;25(4):296–9.

    Article  PubMed  CAS  Google Scholar 

  68. Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology. 2003;45(6):393–9.

    Article  PubMed  Google Scholar 

  69. Chemelli AP, Schocke M, Sperl W, Trieb T, Aichner F, Felber S. Magnetic resonance spectroscopy (MRS) in five patients with treated propionic acidemia. J Magn Reson Imaging. 2000;11(6):596–600.

    Article  PubMed  CAS  Google Scholar 

  70. Bergman AJ, Van der Knaap MS, Smeitink JA, et al. Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia: clinical and biochemical considerations. Pediatr Res. 1996;40(3):404–9.

    Article  PubMed  CAS  Google Scholar 

  71. Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, Zamani AA. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol. 2008;38(10):1054–61.

    Article  PubMed  Google Scholar 

  72. Harting I, Seitz A, Geb S, et al. Looking beyond the basal ganglia: the spectrum of MRI changes in methylmalonic acidaemia. J Inherit Metab Dis. 2008;31(3):368–78.

    Article  PubMed  CAS  Google Scholar 

  73. Lam WW, Wang ZJ, Zhao H, et al. 1 H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis. Neuroradiology. 1998;40(5):315–23.

    Article  PubMed  CAS  Google Scholar 

  74. Trinh BC, Melhem ER, Barker PB. Multi-slice proton MR spectroscopy and diffusion-weighted imaging in methylmalonic acidemia: report of two cases and review of the literature. AJNR Am J Neuroradiol. 2001;22(5):831–3.

    PubMed  CAS  Google Scholar 

  75. Takeuchi M, Harada M, Matsuzaki K, Hisaoka S, Nishitani H, Mori K. Magnetic resonance imaging and spectroscopy in a patient with treated methylmalonic acidemia. J Comput Assist Tomogr. 2003;27(4):547–51.

    Article  PubMed  Google Scholar 

  76. Michel SJ, Given 2nd CA, Robertson Jr WC. Imaging of the brain, including diffusion-weighted imaging in methylmalonic acidemia. Pediatr Radiol. 2004;34(7):580–2.

    Article  PubMed  Google Scholar 

  77. Longo D, Fariello G, Dionisi-Vici C, et al. MRI and 1 H-MRS findings in early-onset cobalamin C/D defect. Neuropediatrics. 2005;36(6):366–72.

    Article  PubMed  CAS  Google Scholar 

  78. Valayannopoulos V, Haudry C, Serre V, et al. New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria. Mitochondrion. 2010;10(4):335–41.

    Article  PubMed  CAS  Google Scholar 

  79. Carrozzo R, Dionisi-Vici C, Steuerwald U, et al. SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain. 2007;130(Pt 3):862–74.

    Article  PubMed  Google Scholar 

  80. Connelly A, Cross JH, Gadian DG, Hunter JV, Kirkham FJ, Leonard JV. Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res. 1993;33(1):77–81.

    Article  PubMed  CAS  Google Scholar 

  81. Kreis R, Ross BD, Farrow NA, Ackerman Z. Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. Radiology. 1992;182(1):19–27.

    PubMed  CAS  Google Scholar 

  82. Ross B, Kreis R, Ernst T. Clinical tools for the 90s: magnetic resonance spectroscopy and metabolite imaging. Eur J Radiol. 1992;14(2):128–40.

    Article  PubMed  CAS  Google Scholar 

  83. Takanashi J, Kurihara A, Tomita M, et al. Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency. Neurology. 2002;59(2):210–4.

    Article  PubMed  CAS  Google Scholar 

  84. Kojic J, Robertson PL, Quint DJ, Martin DM, Pang Y, Sundgren PC. Brain glutamine by MRS in a patient with urea cycle disorder and coma. Pediatr Neurol. 2005;32(2):143–6.

    Article  PubMed  Google Scholar 

  85. Gungor S, Akinci A, Firat AK, Tabel Y, Alkan A. Neuroimaging findings in hyperargininemia. J Neuroimaging. 2008;18(4):457–62.

    Article  PubMed  Google Scholar 

  86. Sijens PE, Reijngoud DJ, Soorani-Lunsing RJ, Oudkerk M, van Spronsen FJ. Cerebral 1 H MR spectroscopy showing elevation of brain guanidinoacetate in argininosuccinate lyase deficiency. Mol Genet Metab. May 2006;88(1):100–2.

    Article  PubMed  CAS  Google Scholar 

  87. Roze E, Azuar C, Menuel C, Haberle J, Guillevin R. Usefulness of magnetic resonance spectroscopy in urea cycle disorders. Pediatr Neurol. 2007;37(3):222–5.

    Article  PubMed  Google Scholar 

  88. Newnham T, Hardikar W, Allen K, et al. Liver transplantation for argininosuccinic aciduria: clinical, biochemical, and metabolic outcome. Liver Transpl. 2008;14(1):41–5.

    Article  PubMed  Google Scholar 

  89. Kanamori K, Ross BD. Glial alkalinization detected in vivo by 1 H-15 N heteronuclear multiple-quantum coherence-transfer NMR in severely hyperammonemic rat. J Neurochem. 1997;68(3):1209–20.

    Article  PubMed  CAS  Google Scholar 

  90. Kanamori K, Bluml S, Ross B. Magnetic resonance spectroscopy in the study of hyperammonemia and hepatic encephalopathy. Adv Exp Med Biol. 1997;420:185–94.

    Article  PubMed  CAS  Google Scholar 

  91. Kanamori K, Ross BD, Chung JC, Kuo EL. Severity of hyperammonemic encephalopathy correlates with brain ammonia level and saturation of glutamine synthetase in vivo. J Neurochem. 1996;67(4):1584–94.

    Article  PubMed  CAS  Google Scholar 

  92. Kanamori K, Ross BD. In vivo activity of glutaminase in the brain of hyperammonaemic rats measured by 15 N nuclear magnetic resonance. Biochem J. 1995;305(Pt 1):329–36.

    PubMed  CAS  Google Scholar 

  93. Kanamori K, Ross BD. 15 N n.m.r. measurement of the in vivo rate of glutamine synthesis and utilization at steady state in the brain of the hyperammonaemic rat. Biochem J. 1993;293(Pt 2):461–8.

    PubMed  CAS  Google Scholar 

  94. Kanamori K, Parivar F, Ross BD. A 15 N NMR study of in vivo cerebral glutamine synthesis in hyperammonemic rats. NMR Biomed. 1993;6(1):21–6.

    Article  PubMed  CAS  Google Scholar 

  95. Geissler A, Kanamori K, Ross BD. Real-time study of the urea cycle using 15N n.m.r. in the isolated perfused rat liver. Biochem J. 1992;287(Pt 3):813–20.

    PubMed  CAS  Google Scholar 

  96. Kanamori K, Ross BD, Farrow NA, Parivar F. A 15 N-NMR study of isolated brain in portacaval-shunted rats after acute hyperammonemia. Biochim Biophys Acta. 1991;1096(4):270–6.

    Article  PubMed  CAS  Google Scholar 

  97. Farrow NA, Kanamori K, Ross BD, Parivar F. A 15 N-n.m.r. study of cerebral, hepatic and renal nitrogen metabolism in hyperammonaemic rats. Biochem J. 1990;270(2):473–81.

    PubMed  CAS  Google Scholar 

  98. Sibson NR, Mason GF, Shen J, et al. In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J Neurochem. 2001;76(4):975–89.

    Article  PubMed  CAS  Google Scholar 

  99. Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG. In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci USA. 1997;94(6):2699–704.

    Article  PubMed  CAS  Google Scholar 

  100. Shen J, Sibson NR, Cline G, Behar KL, Rothman DL, Shulman RG. 15 N-NMR spectroscopy studies of ammonia transport and glutamine synthesis in the hyperammonemic rat brain. Dev Neurosci. 1998;20(4–5):434–43.

    Article  PubMed  CAS  Google Scholar 

  101. Sibson NR, Shen J, Mason GF, Rothman DL, Behar KL, Shulman RG. Functional energy metabolism: in vivo 13C-NMR spectroscopy evidence for coupling of cerebral glucose consumption and glutamatergic neuronalactivity. Dev Neurosci. 1998;20(4–5):321–30.

    Article  PubMed  CAS  Google Scholar 

  102. Elsas LJ. Galactosemia. In: Pagon RA, Bird TC, Dolan CR, eds. GeneReviews [Internet]. October 26, 2010 ed. Seattle, WA: University of Washington; 1993.

    Google Scholar 

  103. Berry GT, Hunter JV, Wang Z, et al. In vivo evidence of brain galactitol accumulation in an infant with galactosemia and encephalopathy. J Pediatr. 2001;138(2):260–2.

    Article  PubMed  CAS  Google Scholar 

  104. Wang ZJ, Berry GT, Dreha SF, Zhao H, Segal S, Zimmerman RA. Proton magnetic resonance spectroscopy of brain metabolites in galactosemia. Ann Neurol. 2001;50(2):266–9.

    Article  PubMed  CAS  Google Scholar 

  105. Otaduy MC, Leite CC, Lacerda MT, et al. Proton MR spectroscopy and imaging of a galactosemic patient before and after dietary treatment. AJNR Am J Neuroradiol. 2006;27(1):204–7.

    PubMed  CAS  Google Scholar 

  106. Moller HE, Ullrich K, Vermathen P, Schuierer G, Koch HG. In vivo study of brain metabolism in galactosemia by 1 H and 31P magnetic resonance spectroscopy. Eur J Pediatr. 1995;154(7 Suppl 2):S8–13.

    Article  PubMed  CAS  Google Scholar 

  107. Mikol J, Vital C, Wassef M, et al. Extensive cortico-subcortical lesions in Wilson’s disease: clinico-pathological study of two cases. Acta Neuropathol. 2005;110(5):451–8.

    Article  PubMed  Google Scholar 

  108. Trocello JM, Guichard JP, Leyendecker A, et al. Corpus callosum abnormalities in Wilson’s disease. J Neurol Neurosurg Psychiatry. 2010;82:1119–21.

    Article  PubMed  Google Scholar 

  109. Van Den Heuvel AG, Van der Grond J, Van Rooij LG, Van Wassenaer-van Hall HN, Hoogenraad TU, Mali WP. Differentiation between portal-systemic encephalopathy and neurodegenerative disorders in patients with Wilson disease: H-1 MR spectroscopy. Radiology. May 1997;203(2):539–43.

    Google Scholar 

  110. Alanen A, Komu M, Penttinen M, Leino R. Magnetic resonance imaging and proton MR spectroscopy in Wilson’s disease. Br J Radiol. 1999;72(860):749–56.

    PubMed  CAS  Google Scholar 

  111. Kraft E, Trenkwalder C, Then Bergh F, Auer DP. Magnetic resonance proton spectroscopy of the brain in Wilson’s disease. J Neurol. 1999;246(8):693–9.

    Article  PubMed  CAS  Google Scholar 

  112. Page RA, Davie CA, MacManus D, et al. Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease. Neurology. 2004;63(4):638–43.

    Article  PubMed  CAS  Google Scholar 

  113. Lucato LT, Otaduy MC, Barbosa ER, et al. Proton MR spectroscopy in Wilson disease: analysis of 36 cases. AJNR Am J Neuroradiol. 2005;26(5):1066–71.

    PubMed  Google Scholar 

  114. Algin O, Taskapilioglu O, Hakyemez B, et al. Structural and neurochemical evaluation of the brain and pons in patients with Wilson’s disease. Jpn J Radiol. 2010;28(9):663–71.

    Article  PubMed  CAS  Google Scholar 

  115. Tarnacka B, Szeszkowski W, Golebiowski M, Czlonkowska A. Brain proton magnetic spectroscopy in long-term treatment of Wilson’s disease patients. Metab Brain Dis. 2010;25(3):325–9.

    Article  PubMed  Google Scholar 

  116. Tarnacka B, Szeszkowski W, Buettner J, Golebiowski M, Gromadzka G, Czlonkowska A. Heterozygous carriers for Wilson’s disease–magnetic spectroscopy changes in the brain. Metab Brain Dis. 2009;24(3):463–8.

    Article  PubMed  CAS  Google Scholar 

  117. Tarnacka B, Szeszkowski W, Golebiowski M, Czlonkowska A. Metabolic changes in 37 newly diagnosed Wilson’s disease patients assessed by magnetic resonance spectroscopy. Parkinsonism Relat Disord. 2009;15(8):582–6.

    Article  PubMed  CAS  Google Scholar 

  118. Tarnacka B, Szeszkowski W, Golebiowski M, Czlonkowska A. MR spectroscopy in monitoring the treatment of Wilson’s disease patients. Mov Disord. 2008;23(11):1560–6.

    Article  PubMed  Google Scholar 

  119. Sinha S, Taly AB, Ravishankar S, Prashanth LK, Vasudev MK. Wilson’s disease: (31)P and (1)H MR spectroscopy and clinical correlation. Neuroradiology. 2010;52(11):977–85.

    Article  PubMed  Google Scholar 

  120. Jayasundar R, Sahani AK, Gaikwad S, Singh S, Behari M. Proton MR spectroscopy of basal ganglia in Wilson’s disease: case report and review of literature. Magn Reson Imaging. 2002;20(1):131–5.

    Article  PubMed  Google Scholar 

  121. Juan CJ, Chen CY, Liu YJ, et al. Acute putaminal necrosis and white matter demyelination in a child with subnormal copper metabolism in Wilson disease: MR imaging and spectroscopic findings. Neuroradiology. 2005;47(6):401–5.

    Article  PubMed  Google Scholar 

  122. Pyne-Geithman GJ, deGrauw TJ, Cecil KM, et al. Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: a case study. Mol Cell Biochem. 2004;262(1–2):35–9.

    Article  PubMed  CAS  Google Scholar 

  123. deGrauw TJ, Cecil KM, Byars AW, Salomons GS, Ball WS, Jakobs C. The clinical syndrome of creatine transporter deficiency. Mol Cell Biochem. 2003;244(1–2):45–8.

    Article  PubMed  CAS  Google Scholar 

  124. Item CB, Stockler-Ipsiroglu S, Stromberger C, et al. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001;69(5):1127–33.

    Article  PubMed  CAS  Google Scholar 

  125. Battini R, Leuzzi V, Carducci C, et al. Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. Mol Genet Metab. 2002;77(4):326–31.

    Article  PubMed  CAS  Google Scholar 

  126. Edvardson S, Korman SH, Livne A, et al. l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. Mol Genet Metab. 2010;101(2–3):228–32.

    Article  PubMed  CAS  Google Scholar 

  127. Johnston K, Plawner L, Cooper L, et al. The second family with AGAT deficiency (Creatine biosynthesis defect): diagnosis, treatment and first prenatal diagnosis. American Society of Human Genetics. Vol Salt Lake City, Utah USA2005:58.

    Google Scholar 

  128. Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S. Creatine deficiency syndromes. In: Pagon RA, Bird TC, Dolan CR, (eds) GeneReviews [Internet]. Jan. 15, 2009 ed. Seattle, WA: University of Washington; 1993.

    Google Scholar 

  129. Stockler S, Holzbach U, Hanefeld F, et al. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res. 1994;36(3):409–13.

    Article  PubMed  CAS  Google Scholar 

  130. Ensenauer R, Thiel T, Schwab KO, et al. Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle. Mol Genet Metab. 2004;82(3):208–13.

    Article  PubMed  CAS  Google Scholar 

  131. Leuzzi V, Bianchi MC, Tosetti M, et al. Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). Neurology. 2000;55(9):1407–9.

    Article  PubMed  CAS  Google Scholar 

  132. Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, et al. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology. 2006;67(3):480–4.

    Article  PubMed  CAS  Google Scholar 

  133. Schulze A, Mayatepek E, Bachert P, Marescau B, De Deyn PP, Rating D. Therapeutic trial of arginine restriction in creatine deficiency syndrome. Eur J Pediatr. 1998;157(7):606–7.

    Article  PubMed  CAS  Google Scholar 

  134. Schulze A, Ebinger F, Rating D, Mayatepek E. Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. Mol Genet Metab. 2001;74(4):413–9.

    Article  PubMed  CAS  Google Scholar 

  135. Schulze A, Hoffmann GF, Bachert P, et al. Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology. 2006;67(4):719–21.

    Article  PubMed  CAS  Google Scholar 

  136. Cecil KM, Salomons GS, Ball Jr WS, et al. Irreversible brain creatine deficiency with elevated serum and urine creatine: a creatine transporter defect? Ann Neurol. 2001;49(3):401–4.

    Article  PubMed  CAS  Google Scholar 

  137. Salomons GS, van Dooren SJ, Verhoeven NM, et al. X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet. 2001;68(6):1497–500.

    Article  PubMed  CAS  Google Scholar 

  138. Puusepp H, Kall K, Salomons GS, et al. The screening of SLC6A8 deficiency among Estonian families with X-linked mental retardation. J Inherit Metab Dis. Jan 10 2009.

    Google Scholar 

  139. Arias A, Corbella M, Fons C, et al. Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening. Clin Biochem. 2007;40(16–17):1328–31.

    Article  PubMed  CAS  Google Scholar 

  140. Betsalel OT, van de Kamp JM, Martinez-Munoz C, et al. Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency. Neurogenetics. 2008;9(3):183–90.

    Article  PubMed  CAS  Google Scholar 

  141. Newmeyer A, Cecil KM, Schapiro M, Clark JF, Degrauw TJ. Incidence of brain creatine transporter deficiency in males with developmental delay referred for brain magnetic resonance imaging. J Dev Behav Pediatr. 2005;26(4):276–82.

    Article  PubMed  Google Scholar 

  142. Rosenberg EH, Almeida LS, Kleefstra T, et al. High prevalence of SLC6A8 deficiency in X-linked mental retardation. Am J Hum Genet. 2004;75(1):97–105.

    Article  PubMed  CAS  Google Scholar 

  143. Lion-Francois L, Cheillan D, Pitelet G, et al. High frequency of creatine deficiency syndromes in patients with unexplained mental retardation. Neurology. 2006;67(9):1713–4.

    Article  PubMed  CAS  Google Scholar 

  144. Almeida LS, Rosenberg EH, Martinez-Munoz C, et al. Overexpression of GAMT restores GAMT activity in primary GAMT-deficient fibroblasts. Mol Genet Metab. 2006;89(4):392–4.

    Article  PubMed  CAS  Google Scholar 

  145. Rosenberg EH, Munoz CM, Degrauw TJ, Jakobs C, Salomons GS. Overexpression of wild-type creatine transporter (SLC6A8) restores creatine uptake in primary SLC6A8-deficient fibroblasts. J Inherit Metab Dis. 2006;29(2–3):345–6.

    Article  PubMed  CAS  Google Scholar 

  146. Clark AJ, Rosenberg EH, Almeida LS, et al. X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Hum Genet. 2006;119(6):604–10.

    Article  PubMed  CAS  Google Scholar 

  147. Pagon RA. GeneTests: an online genetic information resource for health care providers. J Med Libr Assoc. 2006;94(3):343–8.

    PubMed  Google Scholar 

  148. Fons C, Sempere A, Arias A, et al. Arginine supplementation in four patients with X-linked creatine transporter defect. J Inherit Metab Dis. 2008;31(6):724–8.

    Article  PubMed  CAS  Google Scholar 

  149. Valayannopoulos V, Boddaert N, Mention K, et al. Secondary creatine deficiency in ornithine delta-aminotransferase deficiency. Mol Genet Metab. 2009;97(2):109–13.

    Article  PubMed  CAS  Google Scholar 

  150. Pérez-Dueñas B, De La Osa A, Capdevila A, Navarro-Sastre A, Leist A, Ribes A, García-Cazorla A, Serrano M, Pineda M, Campistol J. (2009). Brain injury in glutaric aciduria type I: the value of functional techniques in magnetic resonance imaging. Eur J Paediatr Neurol, 13(6), 534–540.

    Google Scholar 

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Acknowledgments

This work was supported by grants from the National Institutes of Health, NIEHS R01 ES015559, NCI R01 CA112182, and NIMH P50 MH077138. The authors have no competing financial or non-financial interests to declare.

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Authors and Affiliations

  1. Departments of Radiology, Pediatrics, Neuroscience and Environmental Health, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Kim M. Cecil Ph.D.

  2. Departments of Radiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Diana M. Lindquist Ph.D.

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  1. Kim M. Cecil Ph.D.
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Correspondence to Kim M. Cecil Ph.D. .

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  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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Cecil, K.M., Lindquist, D.M. (2013). Metabolic Disorders. 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_11

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