Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy

Abstract

Pyridoxine-dependent epilepsy is a rare, autosomal recessive, treatable cause of neonatal seizures. Genetic testing can confirm mutations in the ALDH7A1 gene, which encodes antiquitin. To avoid delays in initiating treatment while awaiting confirmatory genetic testing, it is recommended that all neonates with unexplained seizures should receive trial of intravenous (IV) pyridoxine to assess for responsiveness. However, oral pyridoxine is not commonly continued in the absence of the typical EEG changes. Two cases are presented that highlight the potential inadequacy of this single-step approach. One neonate ultimately diagnosed with pyridoxine-dependent seizures had no EEG changes after administration of IV pyridoxine. In contrast, another neonate who did not have this diagnosis had profound EEG changes after pyridoxine administration. We present 2 cases that highlight the difficulties in using initial EEG response to IV pyridoxine in establishing a diagnosis of pyridoxine-dependent seizures in the neonate. Given the availability of biochemical markers and gene testing, we suggest that oral pyridoxine treatment should be continued until biochemical and/or genetic testing has confirmed the presence or absence of pyridoxine-dependent epilepsy.

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

“…Our search strategy yielded 497 patients with a confirmed genetic diagnosis of B6-dependent epilepsies. Of these, 90.7% (431/497) were diagnosed with the following three disorders: ALDH deficiency (69.4%), PNPO deficiency (13.2%), and PLPBP deficiency (9.2%) ( Figure 1 ) [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , ...…”

Inborn Errors of Metabolism in Pediatric Epilepsy

“…[4][5][6] This disease is characterized by an error in lysine catabolism as a result of a deficiency in alpha-aminoadipic semialdehyde (AASA) dehydrogenase otherwise known as antiquitin ( Figure). 2,7 Piperideine-6-carboxylate, which inactivates pyridoxal phosphate, subsequently accumulates. Pyridoxal phosphate is the activated form of pyridoxine and a cofactor for numerous reactions and enzymes.…”

“…6 Intravenous pyridoxine has a quick onset of action, though studies have shown that patients who appear to respond to IV pyridoxine by cessation of seizures after administration do not always have true PDE. 7 Often, it is given empirically with unknown etiology of neonatal seizures. Definitive diagnosis is through genetic testing.…”

“…8 Patients' multiple seizure types and vague symptoms including tremors, abdominal distension, emesis, irritability, sleeplessness, hyperalertness, and abnormal eye movements present challenges in diagnosis. 6,7 In some patients the condition may present as looking like hypoxic ischemic injury, a frequent cause of neonatal seizures. 8 Long-term Outcomes.…”

“…Evidence for its use in PDE is mixed but confounded by the fact that genetic testing results are often not reported and patients are on multiple antiseizure medications. Cirillo 7 reported on a case of true PDE diagnosed from genetic testing. This patient born at 38 weeks was initiated on oral pyridoxine on the fifth day of life, which was titrated up to 150 mg once daily while she was being weaned off concomitant phenobarbital.…”