ISSN - 0973-0958
Atypical Pyridoxine Dependent Epilepsy in a Newborn 12/12/2018 00:00:00 https://www.pediatriconcall.com/Journal/images/journal_cover.jpg
   
 
Atypical Pyridoxine Dependent Epilepsy in a Newborn
Ravi Teja Jaladi, Shrabani Mondal, Asim Kumar Mallick, Isita Tripathy.
Department of Pediatrics, NRS Medical College, Kolkata, India.
Cite this article  Copy Citation
Jaladi R T, Mondal S, Mallick A K, Tripathy I. Atypical Pyridoxine Dependent Epilepsy in a Newborn. Pediatr Oncall J. 2019;16. doi: 10.7199/ped.oncall.2019.60

Address for Correspondence
Ravi Teja Jaladi, Department of Pediatrics, NRS Medical College, Kolkata, India.
 
Email
jaladiraviteja@gmail.com
 
Keywords
pyridoxine, epilepsy, encephalopathy, seizures
 
Pyridoxine dependent epilepsy is one kind of refractory seizures which presents as encephalopathy from in utero to late infancy and sometimes into adulthood.1 Pyridoxine dependent epilepsy is an autosomal recessive disorder caused due to abnormality of enzyme glutamic acid decarboxylase which result in reduced synthesis of inhibitory neurotransmitter gamma amino butyric acid (GABA).2 Due to its rarity and the absence of appropriate biochemical tests, the diagnosis of pyridoxine dependent epilepsy is not always easy.3 Though catastrophic, pyridoxine dependent seizures readily respond to administration of pyridoxine with cessation of seizures usually within minutes after administration of pyridoxine. If not identified early, this leads to fatality in most cases and survivors will be left with severe intellectual disability. We present a neonate with a birth weight of 4.3kg delivered via caesarean section who presented to us with uncontrollable seizures on day 7 of life with encephalopathy without any significant antenatal and postnatal history. Baby was normal for 2 days after birth and on day 3 of life mother noticed that baby had staring look, refusal of feeds with involuntary movement of limbs. The baby was then taken to a pediatrician who identified them as seizures and started the child on intravenous (IV) phenobarbitone and IV antibiotics consisting of cefotaxime and amikacin. The child was referred to us on day 7 of life in view of uncontrollable resistant seizures. On presentation to us, child had tonic posturing without up rolling of eyeballs. Systemic examination was normal. On investigations, hemoglobin was 15.5gm/dl, white cell count 9200 cells/cumm (neutrophils 45%, lymphocytes 55%, basophils 5%) and platelet count was 500,000 cells/cumm. Cerebrospinal fluid (CSF) showed protein 85mg/dl (normal upto 120mg/dl), 5-6 mononuclear cells/hpf (normal upto 14 cells/ hpf) and glucose 56mg/dl (corresponding blood sugar was 78mg/dl). CRP was 8.4mg/L (normal upto 15.8mg/L). Serum calcium was 8.8mg/dl (normal 7 to 12mg/dl), magnesium 2.2 meq /L (normal 0.65 to 1.05 meq/L), lactate 4.2mmol/l (normal 1.1 to 2.3 mmol/l) and pyruvate 0.27mg/dl. Blood culture and urine culture did not grow any organism. EEG and MRI brain were normal. The child continued to have uncontrolled seizures for which the child was started on IV phenobarbitone followed by IV phenytoin, IV levetiracetam (increased to a maximum of 60mg/kg/day). But the child deteriorated further requiring mechanical ventilation and injection midazolam infusion but the seizures were not controlled. Antibiotics were upgraded to IV Meropenem and IV Vancomycin on day 2 of admission. A trial of IV pyridoxine was given at 30mg/kg/day on day 3 of hospitalization along with multivitamin infusion and was continued.2 The baby continued to have seizures and finally multivitamin infusion was stopped after 7 days due to non-response. On day 9 of pyridoxine administration, the seizures stopped for the very first time. Unsure of cause of response, anti-epileptics were weaned in the order of Inj levetiracetam followed by Inj phenytoin and finally Inj phenobarbitone. The seizures did not recur even after weaning of all anti-epileptics. We continued pyridoxine suspecting it to be a case of pyridoxine dependent epilepsy. Subsequently pyridoxine was shifted from injectable therapy to oral therapy. During the observation period, mother forgot to administer pyridoxine once and the baby again had seizure for which oral pyridoxine was given and this time the seizures stopped within an hour suggestive of classical pyridoxine dependent seizures.4 Laboratory tests in form pipecolic acid and alpha amino adipic semi aldehyde could not be done due to non-availability.
Infants with classical neonatal pyridoxine dependent seizures have fits soon after birth but other atypical presentations are also reported. Other manifestations include hepatomegaly, visual agnosia, squint, articular apraxia.3 Pyridoxine dependent seizures should be suspected in an infant less than 3 years with seizures with no abnormal antenatal or natal history and a possible elder sibling death due to uncontrollable seizures.5 Baxter proposed a new criteria to diagnose pyridoxine dependent epilepsy which includes (i) seizures cease within 7 days of administration of pyridoxine (ii) recur when pyridoxine supplementation is withdrawn (iii) ceases again when pyridoxine is given again.6 Similarly, our patient had response to pyridoxine after 9 days, had recurrence of seizure on missing a dose and again seizures stopped on giving pyridoxine.
Due to its rarity and in the absence of appropriate biochemical tests the diagnosis of pyridoxine dependent epilepsy is not always easy.3 Early testing of biomarkers including pipecolic acid and alpha amino adipic semi aldehyde may prevent delay in diagnosis of pyridoxine dependent epilepsy.8 We could not do the biomarkers in our patient due to non-availability. Once the diagnosis is confirmed, therapy should be continued indefinitely. The dose of pyridoxine recommended varies from 5 to 300 mg/kg/ day.7
We thus report, that one may need to continue pyridoxine supplementation in pyridoxine dependent seizures for longer time as response can take a longer time.
 
Funding
None
 
Conflict of Interest
None
 
References :
  1. Mohammed AM, Abeer JH. Generalised seizures and other epilepsy syndrome. In: Kliegman RM, Stanton BMD, St. Geme J, Schor NF (eds). Nelson textbook of Paediatrics. 1st South Asia edition. Elsevier. 2016; 593
  2. Sansevere AJ, Bergin AM. Neonatal seizures. In: Eichenwald EC, Hansen AR, Martin CR, Stark AR (eds). Cloherty and Starks Manual of neonatal care. Wolters Kluwer Health. Philadelphia. 2016; 56: 812 - 822.
  3. Lin J, Lin K, Masruha MR, Vilanova LC. Pyridoxine dependent epilepsy initially responsive to phenobarbital. Arq Neuropsiquiatr. 2007; 65: 1026-9.  [CrossRef]  [PubMed]
  4. Koul R. Pyridoxine - dependent seizures: 10-year follow-up of eight cases. Neurol India 2009; 57: 460-3.  [CrossRef]  [PubMed]
  5. Hansen-KN, Ostergaard JR, Møller SM. Pyridoxine dependent seizures. Ugeskr Laeger. 1994;156:6222-4.
  6. Baxter P. Epidemiology of pyridoxine - dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999; 81; 431-433.  [CrossRef]  [PubMed]  [PMC free article]
  7. Haeggenli CA, Girardin E, Paunier L. Pyridoxine dependent seizures, clinical and therapeutic aspects. Eur J Paediatr. 1991; 150: 452-5.  [CrossRef]
  8. Segal EB, Grinspan ZM, Mandel AM, Gospe SM Jr. Biomarkers aiding diagnosis of atypical presentation of pyridoxine dependent epilepsy. Pediatr Neurol. 2011: 44: 289 - 91.  [CrossRef]  [PubMed]

DOI No : https://doi.org/10.7199/ped.oncall.2019.60

Cite this article as: :
Jaladi R T, Mondal S, Mallick A K, Tripathy I. Atypical Pyridoxine Dependent Epilepsy in a Newborn. Pediatr Oncall J. 2019;16. doi: 10.7199/ped.oncall.2019.60
ask a doctor
Ask a Doctor
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
Disclaimer: The information given by www.pediatriconcall.com is provided by medical and paramedical & Health providers voluntarily for display & is meant only for informational purpose. The site does not guarantee the accuracy or authenticity of the information. Use of any information is solely at the user's own risk. The appearance of advertisement or product information in the various section in the website does not constitute an endorsement or approval by Pediatric Oncall of the quality or value of the said product or of claims made by its manufacturer.
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0