Pyridoxine-Dependent Seizures Caused by Alpha Amino Adipic Semialdehyde Dehydrogenase Deficiency: The First Polish Case with Confirmed Biochemical and Molecular Pathology

Abstract

Pyridoxine-dependent seizures are a rare condition recognized when numerous seizures respond to pyridoxine treatment and recur on pyridoxine withdrawal. For decades the diagnosis was confirmed only with pyridoxine treatment withdrawal trial. Recently described biochemical and molecular pathology improved the diagnostic process for those cases in which seizures are caused by alpha amino adipic semialdehyde dehydrogenase deficiency. This article presents a girl with recurrent status epilepticus episodes resistant to phenobarbital and phenytoin and partly responding to midazolam. Eventually the seizures were completely controlled with pyridoxine; however, due to the severe condition of this child when seizing, no trial of withdrawal has been performed. The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated α-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. Due to the availability of reliable laboratory testing, confirmation of the diagnosis was made without the life-threatening trial of pyridoxine withdrawal.

Keywords

pyridoxine-dependent seizures alpha amino adipic semialdehyde dehydrogenase α-AASA dehydrogenase antiquitin

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References

Hunt AD , Stokes J. , McCrory WW , Stroud HH Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics. 1954 ;13(2):140-145.

Plecko B. , Hikel C. , Korenke GC Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy . Neuropediatrics. 2005;36(3):200-205.

Gupta VK , Mishra D. , Mathur I. , Singh KK Pyridoxine-dependent seizures: a case report and a critical review of the literature. J Paediatr Child Health. 2001;37(6):592-596.

Pietz J. , Benninger C. , Schäfer H. et al. Treatment of infantile spasms with high-dosage vitamin B6. Epilepsia. 1993;34(4): 757-763.

Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999;81(5): 431-433.

Bok LA , Struys E. , Willemsen MA et al. Pyridoxine dependent seizures in Dutch patients: diagnosis by elevated urinary alphaaminoadipic semialdehyde dehydrogenase levels. Arch Dis Child. 2006 Nov 6; [Epub ahead of print]

Mills PB , Struys E. , Jakobs C. et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med. 2006;12(3):307-309.

Plecko B. , Paul K. , Paschke E. et al. Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene . Hum Mutat. 2007;28(1):19-26.

Baxter P. Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol. 2001;43(6):416-420.

10.

Coker SB Postneonatal vitamin B6-dependent epilepsy. Pediatrics . 1992;90(2Pt1):221-223.

11.

Ohtsuka Y. , Hattori J. , Ishida T. et al. Long-term follow-up of an individual with vitamin B6-dependent seizures. Dev Med Child Neurol. 1999;41(3):203-206.

12.

Shih JJ , Kornblum H. , Shewmon DA Global brain dysfunction in an infant with pyridoxine dependency: evaluation with EEG, evoked potentials, MRI, and PET. Neurology . 1996;47:824-826.

13.

Gospe SM , Hecht ST Longitudinal MRI findings in pyridoxine dependent seizures. Neurology. 1998;51:74-78.

14.

Baxter P. , Griffiths P. , Kelly T. , Gardner-Medwin D. Pyridoxine-dependent seizures: demographic, clinical, MRI and psychometric features, and effect of dose on intelligence quotient. Dev Med Child Neurol. 1996;38:998-1006.

15.

Schulze-Bonhage A. , Kurthen M. , Walger P. , Elger CE Pharmacorefractory status epilepticus due to low vitamin B6 levels during pregnancy. Epilepsia. 2004;45(1):81-84.

16.

Grillo E. , da Silva RJM , Barbato JH Pyridoxine-dependent seizures responding to extremely low-dose pyridoxine . Dev Med Child Neurol. 2001;43:413-415.

17.

Baynes K. , Farias ST , Gospe SM Pyridoxine-dependent seizures and cognition in adulthood. Dev Med Child Neurol. 2003; 45(11):782-785.

18.

Rankin PM , Harrison S. , Chong WK et al. Pyridoxine-dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regime. Dev Med Child Neurol. 2007;49(4):300-305.

19.

Kirksey A. , Morre DM , Wasynczuk AZ Neuronal development in vitamin B6 deficiency. Ann NY Acad Sci. 1990;585:202-218.

20.

Salomons GS , Bok LA , Struys EA et al. An intriguing "silent" mutation and founder effect in antiquitin (ALDH7A1). Ann Neurol. 2007;62(4):414-418.

21.

Struys EA , Jakobs C. α-aminoadipic semialdehyde is the bio-marker for pyridoxine dependent epilepsy caused by a-aminoadipic semialdehyde dehydrogenase deficiency. Mol Genet Metab. 2007;91(4):405.