Vitamin and Cofactor Responsive Encephalopathies and Seizures

Ingrid Tein


Early diagnosis and treatment vitamin and/or cofactor responsive encephalopathies and seizures is critical for both seizure control and cerebral development and to prevent the kindling of intractable seizures with secondary brain injury. Recognition of these specific disorders is key to their management given their essential requirement for specific cofactors and their reduced responsiveness to standard anticonvulsant therapy. The overall goals of this review are; (1) To provide recognition of the clinical phenotypes of selected treatable metabolic etiologies of early-onset encephalopathies with seizures; (2) To highlight the appropriate diagnostic investigations for each, and (3) To  outline the effective treatment strategies. Each condition will be described followed by an approach to vitamin-responsive infantile-onset seizure management. A list of vitamin/cofactor responsive neurological conditions is provided in Table 1.


vitamin responsive; cofactor responsive; encephalopathies; epilepsy; transporters; energy metabolism

Full Text:



Klepper J, Leiendecker B (2007) GLUT1 deficiency syndrome--2007 update. Dev Med Child Neurol 49 (9):707-16. DOI: 10.1111/j.1469-8749.2007.00707.x PMID: 17718830

De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI (1991) Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 325 (10):703-9. DOI: 10.1056/NEJM199109053251006 PMID: 1714544

Klepper J, Leiendecker B, Bredahl R, Athanassopoulos S, Heinen F, Gertsen E et al. (2002) Introduction of a ketogenic diet in young infants. J Inherit Metab Dis 25 (6):449-60. PMID: 12555938

Klepper J, Scheffer H, Leiendecker B, Gertsen E, Binder S, Leferink M et al. (2005) Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively. Neuropediatrics 36 (5):302-8. DOI: 10.1055/s-2005-872843 PMID: 16217704

Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R et al. (2004) GLUT1 deficiency and other glucose transporter diseases. Eur J Endocrinol 150 (5):627-33. PMID: 15132717

Brockmann K (2009) The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev 31 (7):545-52. DOI: 10.1016/j.braindev.2009.02.008 PMID: 19304421

Klepper J, Flörcken A, Fischbarg J, Voit T (2003) Effects of anticonvulsants on GLUT1-mediated glucose transport in GLUT1 deficiency syndrome in vitro. Eur J Pediatr 162 (2):84-9. DOI: 10.1007/s00431-002-1112-8 PMID: 12548383

Klepper J, Willemsen M, Verrips A, Guertsen E, Herrmann R, Kutzick C et al. (2001) Autosomal dominant transmission of GLUT1 deficiency. Hum Mol Genet 10 (1):63-8. PMID: 11136715

Klepper J, Scheffer H, Elsaid MF, Kamsteeg EJ, Leferink M, Ben-Omran T (2009) Autosomal recessive inheritance of GLUT1 deficiency syndrome. Neuropediatrics 40 (5):207-10. DOI: 10.1055/s-0030-1248264 PMID: 20221955

Schiaffino MC, Bellini C, Costabello L, Caruso U, Jakobs C, Salomons GS et al. (2005) X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation. Neurogenetics 6 (3):165-8. DOI: 10.1007/s10048-005-0002-4 PMID: 16086185

van de Kamp JM, Mancini GM, Pouwels PJ, Betsalel OT, van Dooren SJ, de Koning I et al. (2011) Clinical features and X-inactivation in females heterozygous for creatine transporter defect. Clin Genet 79 (3):264-72. DOI: 10.1111/j.1399-0004.2010.01460.x PMID: 20528887

Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ et al. (2001) X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet 68 (6):1497-500. DOI: 10.1086/320595 PMID: 11326334

Battini R, Chilosi AM, Casarano M, Moro F, Comparini A, Alessandrì MG et al. (2011) Language disorder with mild intellectual disability in a child affected by a novel mutation of SLC6A8 gene. Mol Genet Metab 102 (2):153-6. DOI: 10.1016/j.ymgme.2010.11.005 PMID: 21144783

Chilosi A, Leuzzi V, Battini R, Tosetti M, Ferretti G, Comparini A et al. (2008) Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. Neurocase 14 (2):151-61. DOI: 10.1080/13554790802060821 PMID: 18569740

Chilosi A, Leuzzi V, Battini R, Tosetti M, Ferretti G, Comparini A et al. (2008) Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect. Neurocase 14 (2):151-61. DOI: 10.1080/13554790802060821 PMID: 18569740

Bianchi MC, Tosetti M, Fornai F, Alessandri' MG, Cipriani P, De Vito G et al. (2000) Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 47 (4):511-3. PMID: 10762163

Battini R, Alessandrì MG, Leuzzi V, Moro F, Tosetti M, Bianchi MC et al. (2006) Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. J Pediatr 148 (6):828-30. DOI: 10.1016/j.jpeds.2006.01.043 PMID: 16769397

Schulze A, Battini R (2007) Pre-symptomatic treatment of creatine biosynthesis defects. Subcell Biochem 46 ():167-81. PMID: 18652077

Edvardson S, Korman SH, Livne A, Shaag A, Saada A, Nalbandian R et al. (2010) l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. Mol Genet Metab 101 (2-3):228-32. DOI: 10.1016/j.ymgme.2010.06.021 PMID: 20682460

Stöckler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M et al. (1994) Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 36 (3):409-13. DOI: 10.1203/00006450-199409000-00023 PMID: 7808840

Stöckler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K (1996) Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 58 (5):914-22. PMID: 8651275

Schulze A, Hess T, Wevers R, Mayatepek E, Bachert P, Marescau B et al. (1997) Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. J Pediatr 131 (4):626-31. PMID: 9386672

Schulze A, Ebinger F, Rating D, Mayatepek E (2001) Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. Mol Genet Metab 74 (4):413-9. DOI: 10.1006/mgme.2001.3257 PMID: 11749046

Mercimek-Mahmutoglu S, Dunbar M, Friesen A, Garret S, Hartnett C, Huh L et al. (2012) Evaluation of two year treatment outcome and limited impact of arginine restriction in a patient with GAMT deficiency. Mol Genet Metab 105 (1):155-8. DOI: 10.1016/j.ymgme.2011.09.037 PMID: 22019491

Verbruggen KT, Sijens PE, Schulze A, Lunsing RJ, Jakobs C, Salomons GS et al. (2007) Successful treatment of a guanidinoacetate methyltransferase deficient patient: findings with relevance to treatment strategy and pathophysiology. Mol Genet Metab 91 (3):294-6. DOI: 10.1016/j.ymgme.2007.03.006 PMID: 17466557

Jaeken J, Detheux M, Van Maldergem L, Foulon M, Carchon H, Van Schaftingen E (1996) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74 (6):542-5. PMID: 8758134

Méneret A, Wiame E, Marelli C, Lenglet T, Van Schaftingen E, Sedel F (2012) A serine synthesis defect presenting with a Charcot-Marie-Tooth-like polyneuropathy. Arch Neurol 69 (7):908-11. DOI: 10.1001/archneurol.2011.1526 PMID: 22393170

Tabatabaie L, Klomp LW, Rubio-Gozalbo ME, Spaapen LJ, Haagen AA, Dorland L et al. (2011) Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency. J Inherit Metab Dis 34 (1):181-4. DOI: 10.1007/s10545-010-9249-5 PMID: 21113737

Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E (1997) Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet 34 (7):594-6. PMID: 9222972

de Koning TJ, Klomp LW (2004) Serine-deficiency syndromes. Curr Opin Neurol 17 (2):197-204. PMID: 15021249

de Koning TJ (2006) Treatment with amino acids in serine deficiency disorders. J Inherit Metab Dis 29 (2-3):347-51. DOI: 10.1007/s10545-006-0269-0 PMID: 16763900

de Koning TJ, Klomp LW, van Oppen AC, Beemer FA, Dorland L, van den Berg I et al. (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364 (9452):2221-2. DOI: 10.1016/S0140-6736(04)17596-X PMID: 15610810

Fuchs SA, Dorland L, de Sain-van der Velden MG, Hendriks M, Klomp LW, Berger R et al. (2006) D-serine in the developing human central nervous system. Ann Neurol 60 (4):476-80. DOI: 10.1002/ana.20977 PMID: 17068790

Baumgartner ER, Suormala T, Wick H, Bausch J, Bonjour JP (1985) Biotinidase deficiency: factors responsible for the increased biotin requirement. J Inherit Metab Dis 8 Suppl 1 ():59-64. PMID: 3930842

Singhi P, Ray M (2011) Ohtahara syndrome with biotinidase deficiency. J Child Neurol 26 (4):507-9. DOI: 10.1177/0883073810383018 PMID: 21115748

Kalayci O, Coskun T, Tokatli A, Demir E, Erdem G, Güngör C et al. (1994) Infantile spasms as the initial symptom of biotinidase deficiency. J Pediatr 124 (1):103-4. PMID: 8283357

(1983) Hearing loss in biotinidase deficiency. Lancet 2 (8363):1365-6. PMID: 6139700

Wolf B, Grier RE, Parker WD, Goodman SI, Allen RJ (1983) Deficient biotinidase activity in late-onset multiple carboxylase deficiency. N Engl J Med 308 (3):161. DOI: 10.1056/NEJM198301203080321 PMID: 6848914

Wolf B, Grier RE, Secor McVoy JR, Heard GS (1985) Biotinidase deficiency: a novel vitamin recycling defect. J Inherit Metab Dis 8 Suppl 1 ():53-8. PMID: 3930841

Wolf B, Heard GS, Jefferson LG, Proud VK, Nance WE, Weissbecker KA (1985) Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program. N Engl J Med 313 (1):16-9. DOI: 10.1056/NEJM198507043130104 PMID: 4000223

Wolf B, Heard GS, Weissbecker KA, McVoy JR, Grier RE, Leshner RT (1985) Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol 18 (5):614-7. DOI: 10.1002/ana.410180517 PMID: 4073853

Wolf B: Biotinidase Deficiency. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviews™ Seattle (WA): University of Washington, Seattle; 1993-. 2000 Mar 24 [updated 2011 Mar 15].

Wolf B, Norrgard K, Pomponio RJ, Mock DM, McVoy JR, Fleischhauer K et al. (1997) Profound biotinidase deficiency in two asymptomatic adults. Am J Med Genet 73 (1):5-9. PMID: 9375914

Schulz PE, Weiner SP, Belmont JW, Fishman MA (1988) Basal ganglia calcifications in a case of biotinidase deficiency. Neurology 38 (8):1326-8. PMID: 3399084

Schulz PE, Weiner SP, Belmont JW, Fishman MA (1988) Basal ganglia calcifications in a case of biotinidase deficiency. Neurology 38 (8):1326-8. PMID: 3399084

Desai S, Ganesan K, Hegde A (2008) Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients. Pediatr Radiol 38 (8):848-56. DOI: 10.1007/s00247-008-0904-z PMID: 18545994

Suormala TM, Baumgartner ER, Wick H, Scheibenreiter S, Schweitzer S (1990) Comparison of patients with complete and partial biotinidase deficiency: biochemical studies. J Inherit Metab Dis 13 (1):76-92. PMID: 2109151

Wolf B (2012) Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have". Genet Med 14 (6):565-75. DOI: 10.1038/gim.2011.6 PMID: 22241090

Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E et al. (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127 (5):917-28. DOI: 10.1016/j.cell.2006.09.041 PMID: 17129779

Lanzkowsky P (1970) Congenital malabsorption of folate. Am J Med 48 (5):580-3. PMID: 5450108

Lanzkowsky P, Erlandson ME, Bezan AI (1969) Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification. Blood 34 (4):452-65. PMID: 4980683

Corbeel L, Van den Berghe G, Jaeken J, Van Tornout J, Eeckels R (1985) Congenital folate malabsorption. Eur J Pediatr 143 (4):284-90. PMID: 3987728

Steinschneider M, Sherbany A, Pavlakis S, Emerson R, Lovelace R, De Vivo DC (1990) Congenital folate malabsorption: reversible clinical and neurophysiologic abnormalities. Neurology 40 (8):1315. PMID: 2381546

Zhao R, Min SH, Qiu A, Sakaris A, Goldberg GL, Sandoval C et al. (2007) The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood 110 (4):1147-52. DOI: 10.1182/blood-2007-02-077099 PMID: 17446347

Lasry I, Berman B, Straussberg R, Sofer Y, Bessler H, Sharkia M et al. (2008) A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. Blood 112 (5):2055-61. DOI: 10.1182/blood-2008-04-150276 PMID: 18559978

Shin DS, Mahadeo K, Min SH, Diop-Bove N, Clayton P, Zhao R et al. (2011) Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption. Mol Genet Metab 103 (1):33-7. DOI: 10.1016/j.ymgme.2011.01.008 PMID: 21333572

Steinfeld R, Grapp M, Kraetzner R, Dreha-Kulaczewski S, Helms G, Dechent P et al. (2009) Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am J Hum Genet 85 (3):354-63. DOI: 10.1016/j.ajhg.2009.08.005 PMID: 19732866

Narisawa K, Wada Y, Saito T, Suzuki H, Kudo M (1977) Infantile type of homocystinuria with N5,10-methylenetetrahydrofolate reductase defect. Tohoku J Exp Med 121 (2):185-94. PMID: 847745/p>

Freeman JM, Finkelstein JD, Mudd SH (1975) Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med 292 (10):491-6. DOI: 10.1056/NEJM197503062921001 PMID: 1117892

Shih VE, Salem MZ, Mudd SH, Uhlendorf BW, Adams RD: A new form of homocystinuria due to N(5,10) methylenetetrahydrofolate reductase deficiency. (Abstract) Pediat Res 1972, 6: 395.

Visy JM, Le Coz P, Chadefaux B, Fressinaud C, Woimant F, Marquet J et al. (1991) Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency revealed by stroke in adult siblings. Neurology 41 (8):1313-5. PMID: 1866027

Haworth JC, Dilling LA, Surtees RA, Seargeant LE, Lue-Shing H, Cooper BA et al. (1993) Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers. Am J Med Genet 45 (5):572-6. DOI: 10.1002/ajmg.1320450510 PMID: 8456826

Hyland K, Smith I, Bottiglieri T, Perry J, Wendel U, Clayton PT et al. (1988) Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology 38 (3):459-62. PMID: 3347350

Goyette P, Frosst P, Rosenblatt DS, Rozen R (1995) Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 56 (5):1052-9. PMID: 7726158

Goyette P, Rozen R (2000) The thermolabile variant 677C-->T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum Mutat 16 (2):132-8. DOI: 10.1002/1098-1004(200008)16:2<132::AID-HUMU5>3.0.CO;2-T PMID: 10923034

Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG et al. (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet 7 (4):551. PMID: 7951330

Bass NE, Wyllie E, Cohen B, Joseph SA (1996) Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the risk of severe electrocerebral suppression with intravenous pyridoxine infusion. J Child Neurol 11 (5):422-4. PMID: 8877616

Kroll JS (1985) Pyridoxine for neonatal seizures: an unexpected danger. Dev Med Child Neurol 27 (3):377-9. PMID: 4018433

Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S et al. (2010) Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 133 (Pt 7):2148-59. DOI: 10.1093/brain/awq143 PMID: 20554659

Plecko B, Hikel C, Korenke GC, Schmitt B, Baumgartner M, Baumeister F et al. (2005) Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics 36 (3):200-5. DOI: 10.1055/s-2005-865727 PMID: 15944906

Nabbout R, Soufflet C, Plouin P, Dulac O (1999) Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal Ed 81 (2):F125-9. PMID: 10448181

Hellström-Westas L, Blennow G, Rosén I (2002) Amplitude-integrated encephalography in pyridoxine-dependent seizures and pyridoxine-responsive seizures. Acta Paediatr 91 (8):977-80. PMID: 12222726

Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT (1991) Pyridoxine-dependent epilepsy: EEG investigations and long-term follow-up. Electroencephalogr Clin Neurophysiol 78 (3):215-21. PMID: 1707793

Bankier A, Turner M, Hopkins IJ (1983) Pyridoxine dependent seizures--a wider clinical spectrum. Arch Dis Child 58 (6):415-8. PMID: 6859931

Coker SB (1992) Postneonatal vitamin B6-dependent epilepsy. Pediatrics 90 (2 Pt 1):221-3. PMID: 1641285

Cox R: Errors of lysine metabolism, in MD Valle, AL Beaudet, B Vogelstein, KW Kinzler, SE Antonarakis, AB Ballabio, CR Scriver, B Childs, WS Sly (Eds). The Online Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001

Newgard CB, Hwang PK, Fletterick RJ (1989) The family of glycogen phosphorylases: structure and function. Crit Rev Biochem Mol Biol 24 (1):69-99. DOI: 10.3109/10409238909082552 PMID: 2667896

Hanada K (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta 1632 (1-3):16-30. PMID: 12782147

Ikeda M, Kihara A, Igarashi Y (2004) Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol. Biochem Biophys Res Commun 325 (1):338-43. DOI: 10.1016/j.bbrc.2004.10.036 PMID: 15522238

Ulvi H, Müngen B, Yakinci C, Yoldaş T (2002) Pyridoxine-dependent seizures: long-term follow-up of two cases with clinical and MRI findings, and pyridoxine treatment. J Trop Pediatr 48 (5):303-6. PMID: 12405174

Gospe SM, Hecht ST (1998) Longitudinal MRI findings in pyridoxine-dependent seizures. Neurology 51 (1):74-8. PMID: 9674782

Lott IT, Coulombe T, Di Paolo RV, Richardson EP, Levy HL (1978) Vitamin B6-dependent seizures: pathology and chemical findings in brain. Neurology 28 (1):47-54. PMID: 563538

Baxter P (2001) Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol 43 (6):416-20. PMID: 11409832

Tanaka R, Okumura M, Arima J, Yamakura S, Momoi T (1992) Pyridoxine-dependent seizures: report of a case with atypical clinical features and abnormal MRI scans. J Child Neurol 7 (1):24-8. PMID: 1552147

Jardim LB, Pires RF, Martins CE, Vargas CR, Vizioli J, Kliemann FA et al. (1994) Pyridoxine-dependent seizures associated with white matter abnormalities. Neuropediatrics 25 (5):259-61. DOI: 10.1055/s-2008-1073032 PMID: 7885536

Stockler S, Plecko B, Gospe SM, Coulter-Mackie M, Connolly M, van Karnebeek C 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 (1-2):48-60. DOI: 10.1016/j.ymgme.2011.05.014 PMID: 21704546

Scharer G, Brocker C, Vasiliou V, Creadon-Swindell G, Gallagher RC, Spector E et al. (2010) The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. J Inherit Metab Dis 33 (5):571-81. DOI: 10.1007/s10545-010-9187-2 PMID: 20814824

Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M et al. (2006) Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 12 (3):307-9. DOI: 10.1038/nm1366 PMID: 16491085

Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C et al. (2007) Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat 28 (1):19-26. DOI: 10.1002/humu.20433 PMID: 17068770

Goutières F, Aicardi J (1985) Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants. Ann Neurol 17 (2):117-20. DOI: 10.1002/ana.410170203 PMID: 3977296

Mabry CC, Bautista A, Kirk RF, Dubilier LD, Braunstein H, Koepke JA (1970) Familial hyperphosphatase with mental retardation, seizures, and neurologic deficits. J Pediatr 77 (1):74-85. PMID: 5465362

Horn D, Schottmann G, Meinecke P (2010) Hyperphosphatasia with mental retardation, brachytelephalangy, and a distinct facial gestalt: Delineation of a recognizable syndrome. Eur J Med Genet 53 (2):85-8. DOI: 10.1016/j.ejmg.2010.01.002 PMID: 20080219

Thompson MD, Nezarati MM, Gillessen-Kaesbach G, Meinecke P, Mendoza-Londono R, Mendoza R et al. (2010) Hyperphosphatasia with seizures, neurologic deficit, and characteristic facial features: Five new patients with Mabry syndrome. Am J Med Genet A 152A (7):1661-9. DOI: 10.1002/ajmg.a.33438 PMID: 20578257

Krawitz PM, Schweiger MR, Rödelsperger C, Marcelis C, Kölsch U, Meisel C et al. (2010) Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome. Nat Genet 42 (10):827-9. DOI: 10.1038/ng.653 PMID: 20802478

Gallagher RC, Van Hove JL, Scharer G, Hyland K, Plecko B, Waters PJ et al. (2009) Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 65 (5):550-6. DOI: 10.1002/ana.21568 PMID: 19142996

Bräutigam C, Hyland K, Wevers R, Sharma R, Wagner L, Stock GJ et al. (2002) Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic L-amino acid decarboxylase deficiency. Neuropediatrics 33 (3):113-7. DOI: 10.1055/s-2002-33673 PMID: 12200739

Clayton PT, Surtees RA, DeVile C, Hyland K, Heales SJ (2003) Neonatal epileptic encephalopathy. Lancet 361 (9369):1614. PMID: 12747882

Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, Scambler PJ et al. (2005) Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. Hum Mol Genet 14 (8):1077-86. DOI: 10.1093/hmg/ddi120 PMID: 15772097

Ruiz A, García-Villoria J, Ormazabal A, Zschocke J, Fiol M, Navarro-Sastre A et al. (2008) A new fatal case of pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency. Mol Genet Metab 93 (2):216-8. DOI: 10.1016/j.ymgme.2007.10.003 PMID: 18024216

Cite this article as: Tein I.: Vitamin and cofactor responsive encephalopathies and seizures. JICNA 2015 15:105.




  • There are currently no refbacks.

Copyright (c) 2015 Tein I

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Creative Commons License
Published by the International Child Neurology Association Estd. 1971 © 2004-2017