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Chapter 53 - Magnetic resonance spectroscopy of inborn errors of metabolism

from Section 8 - Pediatrics

Published online by Cambridge University Press:  05 March 2013

By
Alberto Bizzi ,
Gian Marco Castelli  and
Graziella Uziel
Edited by
Jonathan H. Gillard ,
Adam D. Waldman  and
Peter B. Barker
Jonathan H. Gillard
Affiliation:
University of Cambridge
Adam D. Waldman
Affiliation:
Imperial College London
Peter B. Barker
Affiliation:
The Johns Hopkins University School of Medicine
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Summary

Genetics of metabolic diseases

Hereditary inborn errors of metabolism are the results of an enzyme defect involving one or more metabolic pathways. An enzymatic block may act by inducing deficiency of metabolites normally produced beyond the block, by interfering with other metabolic pathways as a result of deviation from normal to accessory or normally unused pathways, by producing accumulation of substances that may interfere with the cell’s function and/or survival, or by interfering in various ways with other essential metabolic processes. Classic genetic disorders are caused by an abnormality in a single gene or may be multifactorial. In addition there are other more recently described categories, such as mitochondrial inheritance, fragile site, and genomic imprinting. Most metabolic diseases are inherited according to single-gene Mendelian mode of inheritance. The inheritance of the phenotypic set follows the Mendelian rules of inheritance: autosomal dominant, autosomal recessive, or X-linked. Canavan (17p), Krabbe (14q), Gaucher (1q), galactosemia (9p), Hallervorden–Spatz (20p), and Wilson (13q) diseases are examples of autosomal recessive single-gene disorders. Adrenoleukodystrophy (ALD), Aicardi syndrome, and Pelizaeus–Merzbacher disease (PMD) are examples of X-linked single-gene disorders. The incidence of single-gene disorders is between 2 and 3% by the age of 1 year, closer to 5% by the age of 25 years.[1] Newborn screening programs are available for single-gene disorders that respond well to dietary therapy, such as phenylalanine hydroxylase deficiency (phenylketonuria [PKU]), galactosemia, and maple syrup urine disease (MSUD). The completion of the Human Genome Mapping Project will make it possible to screen the population for many other single-gene disorders. This novel possibility raises many ethical and legal questions that have yet to be addressed.[2]

Chromosomes are the structures in which genes are packaged. Chromosome disorders are the result of either deficiency or excess of chromosomal material. It is estimated that approximately 5 in 1000 live newborns will have a chromosome abnormality. Deficiency or excess of chromosomal material can be the result of a change in chromosome number (polyploidy, aneuploidy) or in structure.

Type
Chapter
Information
Clinical MR Neuroimaging
Physiological and Functional Techniques
 , pp. 823 - 842
Publisher: Cambridge University Press
Print publication year: 2009

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References

Baird, P, Anderson, T, Newcombe, H, Lowry, R. Genetic disorders in children and young adults: a population study. Am J Hum Genet 1988; 42: 677.Google Scholar
Gilliam, TC, Brzustowicz, LM, Castilla, LH, et al. Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature 1990; 345: 823–825.CrossRefGoogle ScholarPubMed
Dyken, P and Krawiecki, N. Neurodegenerative diseases of infancy and childhood. Ann Neurol 1983; 13: 351–364.CrossRefGoogle ScholarPubMed
van der Knaap, M, Naidu, S, Breiter, S. Alexander disease: diagnosis with MR imaging. AJNR Am J Neuroradiol 2001; 22: 541–552.Google ScholarPubMed
Brenner, M, Johnson, A, Boespflug-Tanguy, O. Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 2001; 27: 117–120.CrossRefGoogle ScholarPubMed
Stockler, S, Holzbach, U, Hanefeld, F, et al. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 1994; 36: 409–413.CrossRefGoogle ScholarPubMed
Wyss, M and Kaddurah-Daouk, R.Creatine and creatinine metabolism. Physiol Rev 2000; 80: 1107–1213.CrossRefGoogle ScholarPubMed
Stockler, S, Hanefeld, F, Frahm, J. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 1996; 348: 789–790.CrossRefGoogle ScholarPubMed
Bianchi, MC, Tosetti, M, Fornai, F, et al. Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 2000; 47: 511–513.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
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: 326–331.CrossRefGoogle Scholar
Cecil, KM, Salomons, GS, Ball, WS, et al. Irreversible brain creatine deficiency with elevated serum and urine creatine: a creatine transporter defect? Ann Neurol 2001; 49: 401–404.CrossRefGoogle ScholarPubMed
Bizzi, A, Bugiani, M, Salomons, GS, et al. X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8. Ann Neurol 2002; 52: 227–231.CrossRefGoogle ScholarPubMed
deGrauw, TJ, Salomons, GS, Cecil, KM, et al. Congenital creatine transporter deficiency. Neuropediatrics 2002; 33: 232–238.CrossRefGoogle ScholarPubMed
Cecil, KM, DeGrauw, TJ, Salomons, GS, et al. Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency. J Comput Assist Tomogr 2003; 27: 44–47.CrossRefGoogle Scholar
Schulze, A, Bachert, P, Schlemmer, H, et al. Lack of creatine in muscle and brain in an adult with GAMT deficiency. Ann Neurol 2003; 53: 248–251.CrossRefGoogle Scholar
Tallan, H, Moore, S, Stein, W. N-Acetyl-l-aspartic acid in brain. J Biol Chem 1956; 219: 257–264.Google ScholarPubMed
Bhakoo, KK, Pearce, D.In vitro expression of N-acetyl aspartate by oligodendrocytes: implications for proton magnetic resonance spectroscopy signal in vivo. J Neurochem 2000; 74: 254–262.CrossRefGoogle ScholarPubMed
Burlina, A, Ferrari, V, Facci, L, Skaper, S, Burlina, A. Mast cells contain large quantities of secretagogue-sensitive N-acetylaspartate. J Neurochem 1997; 69: 1314–1317.CrossRefGoogle ScholarPubMed
Ebisu, T, Rooney, WD, Graham, SH, Weiner, MW, Maudsley, AA. N-Acetylaspartate as an in vivo marker of neuronal viability in kainate-induced status epilepticus: 1H magnetic resonance spectroscopic imaging. J Cereb Blood Flow Metab 1994; 14: 373–382.CrossRefGoogle Scholar
De Stefano, N, Matthews, PM, Arnold, DL. Reversible decreases in N-acetyl aspartate after acute brain injury. Magn Reson Med 1995; 34: 721–727.CrossRefGoogle ScholarPubMed
Bizzi, A, Ulug, AM, Crawford, TO, et al. Quantitative proton MR spectroscopic imaging in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 2001; 22: 1125–1130.Google ScholarPubMed
Clark, JB. N-acetyl aspartate: a marker for neuronal loss or mitochondrial dysfunction. Dev Neurosci 1998; 20: 271–276.CrossRefGoogle ScholarPubMed
Martin, E, Capone, A, Schneider, J, Hennig, J, Thiel, T. Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy? Ann Neurol 2001; 49: 518–521.CrossRefGoogle ScholarPubMed
Canavan, MM. Schilder’s encephalitis periaxialis diffusa. Arch Neurol Psychiatry 1931; 25: 299.CrossRefGoogle Scholar
van Bogaert, L, Bertrand, I. Sur une idiotie familiale avec digénérescence spongieuse du névraxe. Acta Neurol Psychiatr Belg 1949; 49: 572–587.Google Scholar
Gambetti, P, Mellman, WJ, Gonatas, NK. Familial spongy degeneration of the central nervous system (van Bogaert–Bertrand disease). An ultrastructural study. Acta Neuropathol (Berl) 1969; 12: 103–115.CrossRefGoogle Scholar
Matalon, R, Michals, K, Sebesta, D, et al. Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with Canavan disease. Am J Med Genet 1988; 29: 463–471.CrossRefGoogle ScholarPubMed
Grodd, W, Krageloh-Mann, I, Peterson, D, Trefz, F, Harzer, K. In vivo assessment of N-acetylaspartate in brain in spongy degeneration (Canavan disease) by proton spectroscopy. Lancet 1990; 336: 437.CrossRefGoogle Scholar
Barker, PB, Bryan, RN, Kumar, AJ, Naidu, S. Proton NMR spectroscopy of Canavan’s disease. Neuropediatrics 1992; 23: 263–267.CrossRefGoogle ScholarPubMed
Shigematsu, H, Okamura, N, Shimeno, H, et al. Purification and characterization of the heat-stable factors essential for the conversion of lignoceric acid to cerebronic acid and glutamic acid: identification of N-acetyl-l-aspartic acid. J Neurochem 1983; 40: 814–820.CrossRefGoogle Scholar
Kirmani, BF, Jacobowitz, DM, Namboodiri, MA. Developmental increase of aspartoacylase in oligodendrocytes parallels CNS myelination. Brain Res Dev Brain Res 2003; 140: 105–115.CrossRefGoogle ScholarPubMed
Varho, T, Komu, M, Sonninen, P, et al. A new metabolite contributing to N-acetyl signal in 1H MRS of the brain in Salla disease. Neurology 1999; 52: 1668–1672.CrossRefGoogle ScholarPubMed
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: 396–401.CrossRefGoogle ScholarPubMed
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: 393–399.Google Scholar
Harper, PA, Healy, PJ, Dennis, JA. Maple syrup urine disease (branched chain ketoaciduria). Am J Pathol 1990; 136: 1445–1447.Google Scholar
Uziel, G, Savoiardo, M, Nardocci, N. CT and MRI in maple syrup urine disease. Neurology 1988; 38: 486–488.CrossRefGoogle ScholarPubMed
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: 296–299.CrossRefGoogle ScholarPubMed
Kreis, R, Pietz, J, Penzien, J, Herschkowitz, N, Boesch, C. Identification and quantitation of phenylalanine in the brain of patients with phenylketonuria by means of localized in vivo 1H magnetic-resonance spectroscopy. J Magn Reson B 1995; 107: 242–251.CrossRefGoogle ScholarPubMed
Leuzzi, V, Bianchi, MC, Tosetti, M, et al. Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria. J Inherit Metab Dis 2000; 23: 563–570.CrossRefGoogle ScholarPubMed
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: 629–635.Google ScholarPubMed
Burgeois, M, Goutieres, F, Chretien, D, et al. Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome. Brain Dev 1992; 14: 404–408.CrossRefGoogle ScholarPubMed
Moroni, I, Bugiani, M, Bizzi, A, et al. Cerebral white matter involvement in children with mitochondrial encephalopathies. Neuropediatrics 2002; 33: 79–85.CrossRefGoogle ScholarPubMed
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: 38–46.CrossRefGoogle ScholarPubMed
Bizzi, A, Danesi, U, Bugiani, M, et al. Incidence of cerebral lactic acidosis in children with mitochondrial encephalomyopathy. In Proceedings of the 10th Annual Meeting of the International Society for Magnetic Resonance in Medicine, Honolulu, 2002.Google Scholar
Frahm, J and Hanefeld, F. Localized proton magnetic resonance spectroscopy of brain disorders in childhood. In Magnetic Resonance Spectroscopy and Imaging in Neurochemistry, ed. Bachelard, H.New York: Plenum Press. 1997; pp. 329–402.CrossRefGoogle Scholar
Parfait, B, Chretien, D, Rotig, A, et al. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum Genet 2000; 106: 236–243.CrossRefGoogle Scholar
Bourgeron, T, Rustin, P, Chretien, D, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995; 11: 144–149.CrossRefGoogle ScholarPubMed
Farina, LC, Uziel, L, Bugiani, G, et al. MR findings in Leigh syndrome with COX deficiency and SURF-1 mutations. AJNR Am J Neuroradiol 2002; 23: 1095–1100.Google ScholarPubMed
van der Knaap, MS, Wevers, RA, Struys, EA, et al. Leukoencephalopathy associated with a disturbance in the metabolism of polyols. Ann Neurol 1999; 46: 925–928.3.0.CO;2-J>CrossRefGoogle Scholar
Barkovich, AJ, Good, WV, Koch, TK, Berg, BO. Mitochondrial disorders: analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol 1993; 14: 1119–1137.Google ScholarPubMed
Savoiardo, M, Ciceri, E, D’Incerti, L, Uziel, G, Scotti, G. Symmetric lesions of the subthalamic nuclei in mitochondrial encephalopathies: an almost distinctive mark of Leigh disease with COX deficiency. AJNR Am J Neuroradiol 1995; 16: 1746–1747.Google ScholarPubMed
Valanne, L, Ketonen, L, Majander, A, Suomalainen, A, Pihko, H. Neuroradiologic findings in children with mitochondrial disorders. AJNR Am J Neuroradiol 1998; 19: 369–377.Google ScholarPubMed
Wilichowski, E, Pouwels, PJ, Frahm, J, Hanefeld, F. Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS. Neuropediatrics 1999; 30: 256–263.CrossRefGoogle ScholarPubMed
Cross, JH, Connelly, A, Gadian, DG, et al. Clinical diversity of pyruvate dehydrogenase deficiency. Pediatr Neurol 1994; 10: 276–283.CrossRefGoogle ScholarPubMed
Cross, JH, Gadian, DG, Connelly, A, Leonard, JV. Proton magnetic resonance spectroscopy studies in lactic acidosis and mitochondrial disorders. J Inherit Metab Dis 1993; 16: 800–811.CrossRefGoogle ScholarPubMed
Krageloh-Mann, I, Grodd, W, Schoning, M, et al. Proton spectroscopy in five patients with Leigh’s disease and mitochondrial enzyme deficiency. Dev Med Child Neurol 1993; 35: 769–776.CrossRefGoogle ScholarPubMed
Lin, DD, Crawford, TO, Barker, PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol 2003; 24: 33–41.Google ScholarPubMed
Nissenkorn, A, Zeharia, A, Lev, D, et al. Neurologic presentations of mitochondrial disorders. J Child Neurol 2000; 15: 44–48.CrossRefGoogle Scholar
Takanashi, J, Sugita, K, Osaka, H. Proton MR spectroscopy in Pelizaeus–Merzbacher disease. AJNR Am J Neuroradiol 1997; 18: 533–535.Google ScholarPubMed
Spalice, A, Popolizio, T, Parisi, P, Scarabino, T, Iannetti, P. Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease. Pediatr Radiol 2000; 30: 171–175.CrossRefGoogle ScholarPubMed
Bonavita, S, Schiffmann, R, Moore, DF, et al. Evidence for neuroaxonal injury in patients with proteolipid protein gene mutations. Neurology 2001; 56: 785–788.CrossRefGoogle ScholarPubMed
Takanashi, J, Inoue, K, Tomita, M, et al. Brain N-acetylaspartate is elevated in Pelizaeus–Merzbacher disease with PLP1 duplication. Neurology 2002; 58: 237–241.CrossRefGoogle ScholarPubMed
D’Incerti, L, Farina, L, Moroni, I, Uziel, G, Savoiardo, M. l-2-Hydroxyglutaric aciduria: MRI in seven cases. Neuroradiology 1998; 40: 727–733.Google ScholarPubMed
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: 614–616.CrossRefGoogle Scholar
van der Knaap, MS, Bakker, HD, Valk, J. MR imaging and proton spectroscopy in 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency. AJNR Am J Neuroradiol 1998; 19: 378–382.Google ScholarPubMed

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