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Monatsschrift Kinderheilkunde

, Volume 160, Issue 8, pp 723–733 | Cite as

Metabolische Epilepsien mit spezifischen Therapieoptionen

Diagnostischer Leitfaden
  • B. PleckoEmail author
Leitthema

Zusammenfassung

Bei therapieresistenten Anfällen müssen, unabhängig vom jeweiligen Lebensalter, angeborene Stoffwechselerkrankungen erwogen werden. Nur selten liegen hierbei erkennbare Epilepsiesyndrome mit typischem EEG-Muster (EEG: Elektroenzephalographie) oder wegweisende Begleitbefunde in Klinik oder kranialer Bildgebung vor. Für zahlreiche metabolisch bedingte Epilepsien existiert ein kausaler Therapieansatz, z. B. durch gezielte Substitution von Vitaminen, Aminosäuren oder alternativen Energieträgern. Dabei entscheidet ein früher Therapiebeginn wesentlich über das Langzeit-Outcome. Der vorliegende Beitrag soll durch die Beschreibung des klinischen Phänotyps, der Anfallssemiologie sowie der diagnostischen Biomarker und Enzymdefekte einen Leitfaden für die Früherkennung behandelbarer metabolischer Epilepsien im Klinikalltag bieten.

Schlüsselwörter

Vitamine Molybdän Spezifische Therapieoptionen Serin Kreatin 

Metabolic epilepsies with specific therapy options

Diagnostic guideline

Abstract

In the presence of therapy-resistant seizures of any age, genetic metabolic diseases have to be considered. Rarely they present with recognizable epileptic syndromes, typical EEG features or clinical and radiologic hallmarks. For many metabolic epilepsies, there is causal treatment available, e.g., pharmacologic doses of selected vitamins, amino acid substitution or by providing alternate energy substrates. Early recognition and initiation of specific treatment is crucial to prevent irreversible brain damage. This article aims to provide a detailed description of selected clinical phenotypes, seizure semiology, diagnostic biomarkers, and enzyme defects in order to enable early recognition of treatable metabolic epilepsies in daily clinical practice.

Keywords

Vitamins Molybdenum Specific therapeutic options Serine Creatine 

Notes

Interessenkonflikt

Die korrespondierende Autorin gibt an, dass kein Interessenkonflikt besteht.

Literatur

  1. 1.
    Baxter P (2001) Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol 43:416–420PubMedCrossRefGoogle Scholar
  2. 2.
    Bok LA, Been JV, Struys EA et al (2010) Antenatal treatment in two Dutch families with pyridoxine-dependent seizures. Eur J Pediatr 169:297–303PubMedCrossRefGoogle Scholar
  3. 3.
    Bok LA, Maurits NM, Willemsen MA et al (2010) The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. Epilepsia 51:2406–2411PubMedCrossRefGoogle Scholar
  4. 4.
    Clayton PT, Surtees RA, DeVile C et al (2003) Neonatal epileptic encephalopathy. Lancet 361:1614PubMedCrossRefGoogle Scholar
  5. 5.
    DeVivo DC, Trifiletti RR, Jacobson RL et al (1991) Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 325:703–709CrossRefGoogle Scholar
  6. 6.
    Footitt EJ, Heales SJ, Mills PB et al (2011) Pyridoxal 5’-phosphate in cerebrospinal fluid; factors affecting concentration. J Inherit Metab Dis 34:529–538PubMedCrossRefGoogle Scholar
  7. 7.
    Gallagher RC, Van Hove JL, Scharer G et al (2009) Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 65:550–556PubMedCrossRefGoogle Scholar
  8. 8.
    Gennip AH van, Abeling NG, Stroomer AE et al (1994) The detection of molybdenum cofactor deficiency: clinical symptomatology and urinary metabolite profile. J Inherit Metab Dis 17:142–145PubMedCrossRefGoogle Scholar
  9. 9.
    Koning TJ de, Poll-The BT, Jaeken J (1999) Continuing education in neurometabolic disorders – serine deficiency disorders. Neuropediatrics 30:1–4PubMedCrossRefGoogle Scholar
  10. 10.
    Hinnell C, Samuel M, Alkufri F et al (2011) Creatine deficiency syndromes: diagnostic pearls and pitfalls. Can J Neurol Sci 38:765–767PubMedGoogle Scholar
  11. 11.
    Hoffmann GF, Schmitt B, Windfuhr M et al (2007) Pyridoxal 5’-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis 30:96–99PubMedCrossRefGoogle Scholar
  12. 12.
    Hunt AD Jr, Stokes J Jr, McCrory WW, Stroud HH (1954) Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 13(2):140–145PubMedGoogle Scholar
  13. 13.
    Hyland K, Buist NR, Powell BR et al (1995) Folinic acid responsive seizures: a new syndrome? J Inherit Metab Dis 18:177–181PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson JL, Duran R (2001) Molydbenum cofactor and isolated sulfite oxidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (Hrsg) The metabolic and molecular basis of inherited disease. McGraw Hill, New York, S 3163–3177Google Scholar
  15. 15.
    Leary L, Wang D, Nordli D et al (2003) Seizure characterisation and electroencephalographic features in glut-1-deficiency syndrome. Epilepsia 44:701–707PubMedCrossRefGoogle Scholar
  16. 16.
    Mills PB, Struys E, Jakobs C et al (2006) Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 12:307–309PubMedCrossRefGoogle Scholar
  17. 17.
    Mills PB, Footitt EJ, Mills KA et al (2010) Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 133:2148–2159PubMedCrossRefGoogle Scholar
  18. 18.
    Mills PB, Footitt EJ, Ceyhan S et al (2012) Urinary AASA excretion is elevated in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency. J Inherit Metab Dis Mar 9. [Epub ahead of print]Google Scholar
  19. 19.
    Mullen SA, Suls A, De Jonghe P, Berkovic SF et al (2010) Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. Neurology 75:432–440PubMedCrossRefGoogle Scholar
  20. 20.
    Plecko B (2004) Treatable metabolic epileptic encephalopathies. In: Engelke UF, Moolenaar SH, Wevers RA (Hrsg) Brain metabolism revisited – concepts and treatment – metabolic epileptic encephalopathies. Int. Symposium ‚Focus on Neuropediatrics‘ 2004, Fulda. SPS, HeilbronnGoogle Scholar
  21. 21.
    Plecko B, Stöckler S (2009) Vitamin B6 dependent seizures. Can J Neurol Sci [Suppl 2] 36:73–77 Google Scholar
  22. 22.
    Plecko B, Hikel C, Korenke G et al (2005) Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics 36:200–205PubMedCrossRefGoogle Scholar
  23. 23.
    Schmitt B, Baumgartner M, Mills PB et al (2010) Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency. Dev Med Child Neurol 52:133–142CrossRefGoogle Scholar
  24. 24.
    Stöckler-Ipsiroglu S, Plecko B (2009) Metabolic epilepsies: approaches to a diagnostic challenge. Can J Neurol Sci [Suppl 2] 36:67–72 Google Scholar
  25. 25.
    Stockler S, Plecko B, Gospe SM Jr et al (2011) Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 104:48–60 PubMedCrossRefGoogle Scholar
  26. 26.
    Stromberger C, Bodamer OA, Stoeckler-Ipsiroglu S et al (2003) Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. J Inherit Metab Dis 26:299–308PubMedCrossRefGoogle Scholar
  27. 27.
    Surtees R, Wolf NI (2007) Treatable neonatal epilepsy. Arch Dis Child 92:659–661PubMedCrossRefGoogle Scholar
  28. 28.
    Tabatabaie L, Klomp LW, Rubio-Gozalbo ME et al (2011) Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency. J Inherit Metab Dis 34:181–184PubMedCrossRefGoogle Scholar
  29. 29.
    Veldman A, Santamaria-Araujo JA, Sollazzo S et al (2010) Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics 125:1249–1254CrossRefGoogle Scholar
  30. 30.
    Vigevano F, Bartuli A (2002) Infantile epileptic syndromes and metabolic etiologies. J Child Neurol [Suppl 3] 17:3S9–14Google Scholar
  31. 31.
    Wolf NI, Bast T, Surtees R (2005) Epilepsy in inborn errors of metabolism. Epileptic Disord 7:67–81PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Extraordinariat NeurologieKinderspital Zürich, Universität ZürichZürichSchweiz

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