Abstract

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range <2), and bilateral symmetrical temporal lobe hemorrhages and thalamic changes on cranial MRI. She developed multifocal and myoclonic seizures refractory to multiple antiepileptic drugs that responded to pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Links

Publisher Full Text

Authors

Mercimek-Mahmutoglu S, Horvath GA, Coulter-Mackie M, Nelson T, Waters PJ, Sargent M, Struys E, Jakobs C, Stockler-Ipsiroglu S, Connolly MB

Institution

Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia, Vancouver, Canada. saadet.mahmutoglu@sickkids.ca

Source

Pediatrics 129:5 2012 May pg e1368-72

MeSH

2-Aminoadipic Acid
Acidosis, Lactic
Aldehyde Dehydrogenase
Alleles
Anticonvulsants
Brain
DNA Mutational Analysis
Diffusion Magnetic Resonance Imaging
Electroencephalography
Epilepsy
Female
Follow-Up Studies
Heterozygote Detection
Humans
Hypoglycemia
Infant
Infant, Newborn
Infusions, Intravenous
Magnetic Resonance Imaging
Mutation, Missense
Pyridoxine
Temporal Lobe
Thalamus

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22529283