Metabolik Epilepsiler
Özet
Doğumsal metabolik hastalıklar, 1/2000 sıklıkta görülen ve %40-60 oranında nöbetlerin birincil veya ikincil bulgu olarak ortaya çıktığı nadir hastalıklardır. Tanımlanamayan veya tedaviye dirençli nöbetler, ensefalopati, akraba evliliği veya ailede benzer öykü varlığında metabolik epilepsiler öncelikle düşünülmelidir. Tanı, klinik şüphe ile başlayan süreçte biyokimyasal ve genetik testlerle kesinleştirilmektedir. Erken dönemde spesifik diyet veya kofaktör tedavileri ile nöbetlerin kontrol altına alınması ve nörolojik sekellerin önlenmesi mümkündür.
Inborn metabolic diseases are rare conditions observed with a frequency of 1/2000, where seizures present as a primary or secondary symptom in 40-60% of cases. Metabolic epilepsies should be prioritized in the differential diagnosis of unexplained or refractory seizures, encephalopathy, or in cases involving parental consanguinity and familial history. Diagnosis is confirmed through biochemical and genetic testing following clinical suspicion. Prompt implementation of specific dietary interventions or cofactor therapies is critical for seizure control and the prevention of long-term neurological damage.
Referanslar
Saudubray JM: Clinical approach to inborn errors of metabolism in paediatrics. In: Saudubray JM, van den Berghe G, Walter JH. Inborn metabolic diseases, 5th edition. Berlin: Springer, 1: 3-54;2012.
Rakhade SN, Jensen FE:Epileptogenesis in the immature brain: emerging mechanisms. Rev Neurol 2009; 5: 380-9.
Pascual J, Campistol J, Gil Nagel A: Epilepsy in inherited metabolic disorders. The Neurologist 2008;14: 1-11.
van Karnebeek CDM, Sayson B, Lee JJY, et al. Metabolic evaluation of epilepsy: a diagnostic algorithm with focus on treatable conditions. Front Neurol. 2018;9:1016.
Lin Lin Lee V,KarMeng Choo B, Chung YS, P Kundap U,Kumari Y, Shaikh MF. Treatment, therapy and management of metabolic epilepsy: a systematic review. Int J MolSci. 2018;19:871
Tumiene B, Peterlin B,Maver A, Utkus A. Contemporary scope of inborn errors of metabolism involving epilepsy or seizures. Metab Brain Dis. 2018;33:1781–6.
Gökben S, Serin HM. Kalıtsal metabolik epilepsiler. Kumandaş S, Canpolat M,editörler.Çocukluk Çağı Epilepsileri. 1. Baskı. Ankara: Türkiye Klinikleri; 2020.p.64-71.
Sharma S, Prasad AN. Inborn errors of metabolism and epilepsy:Current understanding,diagnosis and treatment approaches.2017;201718(7):e1384
Papetti, L.; Parisi, P.; Leuzzi, V.; Nardecchia, F.; Nicita, F.; Ursitti, F.; Marra, F.; Paolino, M.C.; Spalice, A. Metabolic epilepsy: An update. Brain Dev. 2013;35: 827–841
Pearl, P:The Top 10 Diagnoses You cannot Afford to Miss. In Inherited metabolic epilepsies Pearl P Ed. Demos Medical Publishing, LLC. New York 2013.
Reddy, C., & Saini, A. G. Metabolic Epilepsy. The Indian Journal of Pediatrics, 2020;16:1-8.
Dulac, O.; Plecko, B.; Gataullina, S.;Wolf, N.I. Occasional seizures, epilepsy, and inborn errors of metabolism. Lancet Neurol. 2014;13: 727–39.
Van Karnebeek, C.D.; Jaggumantri, S. Current treatment and management of pyridoxine-dependent epilepsy. Curr. Treat. Options Neurol. 2015; 17: 335.
Rahman S, Footitt E, Varadkar S, Clayton P: Inborn errors of metabolism causing epilepsy. Dev Med Child Neurol 2013; 55:23-36.
Gallagher RC, Van Hove JL, Scharer G, et al.: Folinic acid responsive seizures are identical to pyridoxine dependent epilepsy. Ann Neurol 2009; 65: 550-6.
Mills, P.B.; Surtees, R.A.; Champion, M.P.; Beesley, C.E.; Dalton, N.; Scambler, P.J.; Heales, S.J.; Briddon, A.;Scheimberg, I.; Hoffmann, G.F.; et al. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 50-phosphate oxidase. Hum. Mol. Genet. 2005; 14: 1077–86.
Hyland, K.; Buist, N.R.; Powell, B.R.; Hoffman, G.F.; Rating, D.; McGrath, J.; Acworth, I.N. Folinic acid responsive seizures: A new syndrome? J. Inherit. Metab. Dis. 1995;18: 177–81.
Wolf B: The neurology of biotinidase deficiency. Mol Genet Metab 104: 27-34;2011
Wang D, Pascual JM, De Vivo D. Glucose transporter type 1 deficiency syndrome. In: Pagon RA, Bird TD, Dolan CR,Stephens K, Adam MP, editors. GeneReviewse [Internet]. Seattle (WA): University of Washington, Seattle;2009. p. 1993–2002. Bookshelf ID: NBK1430.)
Campistol, J.; Plecko, B. Treatable newborn and infant seizures due to inborn errors of metabolism. Epileptic Disord. 2015;17: 229–42.
Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol 2010;42:163–71
Stockler-Ipsiroglu, S.; van Karnebeek, C.D. Cerebral creatine deficiencies: A group of treatable intellectualdevelopmental disorders. Semin. Neurol. 2014; 34: 350–56.
Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol 2007;22:606–16.
Patel, J.; Mercimek-Mahmutoglu, S. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes. Indian J. Pediatr. 2016; 83: 1164–74.
Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjold M, Wedell A et al. Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am. J. Hum. Genet.2014; 95: 285–93
Verrotti, A.; Carelli, A.; Coppola, G. Epilepsy in children with Menkes disease: A systematic review of literature. J. Child Neurol. 2014;29: 1757–64
Van Hove, J.L.; Lohr, N.J. Metabolic and monogenic causes of seizures in neonates and young infants. Mol. Genet. Metab. 2011;104:214–30.
Koch, J.; Mayr, J.A.; Alhaddad, B.; Rauscher, C.; Bierau, J.; Kovacs-Nagy, R.; Coene, K.L.; Bader, I.; Holzhacker, M.; Prokisch, H.; et al. CAD mutations and uridine-responsive epileptic encephalopathy.Brain 2017;140: 279–86.
Fiumara, A.; Barone, R.; Del Campo, G.; Striano, P.; Jaeken, J. Electroclinical Features of Early-Onset Epileptic Encephalopathies in Congenital Disorders of Glycosylation (CDGs). JIMD Rep. 2015; 27, 93–9.
Wolf NI, Garcı´a-Cazorla A, Hoffmann GF. Epilepsy and inborn errors of metabolism in children. J Inherit Metab Dis 2009; 32:609–17.
Monaghan TS, Delanty N. Lafora disease: epidemiology, pathophysiology and management. CNS Drugs 2010; 24:549–61.
Finsterer J. Central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand 2006; 114:217–38.
Wolf NI, Rahman S, Schmitt B, Taanman JW, Duncan AJ, Harting I, et al. Status epilepticus in children with Alpers disease caused by POLG1 mutations: EEG and MRI features. Epilepsia 2009; 50:1596–607.
Rahman S,Clarke CF, Hirano M: ENMC International Workshop diagnosis and treatment of coenzyme Q10 deficiency. Neuromuscul Disord 2012;22:76-86.
