Download PDF
Neuropediatrics 2018; 49(02): 154-157
DOI: 10.1055/s-0037-1621721
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Antiquitin Deficiency with Adolescent Onset Epilepsy: Molecular Diagnosis in a Mother of Affected Offsprings

Rangan Srinivasaraghavan
1   Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2   Department of Pediatrics, Mahatma Gandhi Medical College and Research Institute, Puducherry, India
,
Narayanan Parameswaran
1   Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
,
Deborah Mathis
3   Division of Clinical Chemistry and Biochemistry, University Childreńs Hospital, Zurich, Switzerland
,
Celine Bürer
4   Division of Metabolic Diseases, University Children's Hospital, Zurich, Switzerland
,
Barbara Plecko
5   Division of Child Neurology, University Childreńs Hospital, Zurich, Switzerland
6   RadiZ-Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Switzerland
7   Division of General Pediatrics, University Children's Hospital Graz, Graz, Austria
› Author Affiliations
Further Information

Publication History

14 September 2017

10 December 2017

Publication Date:
05 February 2018 (online)

    Permissions and Reprints

Abstract

Antiquitin deficiency is the most prevalent form of pyridoxine-dependent epilepsy. While most patients present with neonatal onset of therapy-resistant seizures, a few cases with late-onset during infancy have been described. Here, we describe the juvenile onset of epilepsy at the age of 17 years due to antiquitin deficiency in an Indian female with homozygosity for the most prevalent ALDH7A1 missense mutation, c.1279G > C; p.Glu427Gln in exon 14. The diagnosis was established along familial cosegregation analysis for an affected offspring, that had neonatal pyridoxine responsive seizures and had been found to be compound heterozygous for c.1279G > C; p.Glu427Gln in exon 14 and a nonsense mutation c.796C > T; p.Arg266* in exon 9. While seizures in the mother had been incompletely controlled by levetiracetam, she remained seizure-free on pyridoxine monotherapy, 200 mg/day. Her fourth pregnancy resulted in a female affected offspring, who was treated prospectively and never developed seizures with a normal outcome at age 2 years while on pyridoxine. This report illustrates that the phenotypic spectrum of antiquitin deficiency is still underestimated and that this treatable inborn error of metabolism has to be considered in case of therapy-resistant seizures even at older age. It furthermore supports prospective in utero treatment with pyridoxine in forthcoming pregnancies at risk.

Keywords

late-onset - genotype -phenotype - intrauterine treatment - prenatal - PDE - therapy resistance
 

  • References

  • 1 Stockler S, Plecko B, Gospe Jr SM. , et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 2011; 104 (1-2): 48-60
    Google Scholar
  • 2 Samanta D. A 15-year-old with seizures: late diagnosis of pyridoxine-dependent epilepsy. Acta Neurol Belg 2016; 116 (04) 667-669
    CrossrefPubMedGoogle Scholar
  • 3 Mills PB, Struys E, Jakobs C. , et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 2006; 12 (03) 307-309
    Google Scholar
  • 4 Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis 2006; 29 (2-3): 317-326
    CrossrefPubMedGoogle Scholar
  • 5 Mills PB, Footitt EJ, Mills KA. , et al. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 2010; 133 (Pt 7): 2148-2159
    CrossrefPubMedGoogle Scholar
  • 6 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 (01) 19-26
    Google Scholar
  • 7 van Karnebeek CDM, Stockler-Ipsiroglu S, Jaggumantri S. , et al. Lysine-restricted diet as adjunct therapy for pyridoxine-dependent epilepsy: the PDE consortium consensus recommendations. JIMD Rep 2014; 15: 1-11
    PubMedGoogle Scholar
  • 8 Rankin PM, Harrison S, Chong WK, Boyd S, Aylett SE. Pyridoxine-dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regime. Dev Med Child Neurol 2007; 49 (04) 300-305
    CrossrefPubMedGoogle Scholar
  • 9 Bok LA, Been JV, Struys EA, Jakobs C, Rijper EAM, Willemsen MA. Antenatal treatment in two Dutch families with pyridoxine-dependent seizures. Eur J Pediatr 2010; 169 (03) 297-303
    CrossrefPubMedGoogle Scholar
  • 10 Bennett CL, Chen Y, Hahn S, Glass IA, Gospe Jr SM. Prevalence of ALDH7A1 mutations in 18 North American pyridoxine-dependent seizure (PDS) patients. Epilepsia 2009; 50 (05) 1167-1175
    CrossrefPubMedGoogle Scholar
  • 11 Marguet F, Barakizou H, Tebani A. , et al. Pyridoxine-dependent epilepsy: report on three families with neuropathology. Metab Brain Dis 2016; 31 (06) 1435-1443
    CrossrefPubMedGoogle Scholar
  • 12 Scharer G, Brocker C, Vasiliou V. , et al. The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. J Inherit Metab Dis 2010; 33 (05) 571-581
    CrossrefPubMedGoogle Scholar
  • 13 Coulter-Mackie MB, Tiebout S, van Karnebeek C, Stockler S. Overexpression of recombinant human antiquitin in E. coli: partial enzyme activity in selected ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy. Mol Genet Metab 2014; 111 (04) 462-466
    CrossrefPubMedGoogle Scholar
  • 14 Mills PB, Camuzeaux SSM, Footitt EJ. , et al. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome. Brain 2014; 137 (Pt 5): 1350-1360
    CrossrefPubMedGoogle Scholar
  • 15 Al Teneiji A, Bruun TUJ, Cordeiro D. , et al. Phenotype, biochemical features, genotype and treatment outcome of pyridoxine-dependent epilepsy. Metab Brain Dis 2017; 32 (02) 443-451
    CrossrefPubMedGoogle Scholar
  • 16 Rutherfurd SM, Bains K, Moughan PJ. Available lysine and digestible amino acid contents of proteinaceous foods of India. Br J Nutr 2012; 108 (Suppl. 02) S59-S68
    CrossrefPubMedGoogle Scholar