title: Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.
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.
authors.affiliation: Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia, Vancouver, Canada. saadet.mahmutoglu@sickkids.ca
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
authors.forename: Gabriella A
authors.initials: GA
authors.lastname: Horvath
authors.forename: Marion
authors.initials: M
authors.lastname: Coulter-Mackie
authors.forename: Tanya
authors.initials: T
authors.lastname: Nelson
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Waters
authors.forename: Michael
authors.initials: M
authors.lastname: Sargent
authors.forename: Eduard
authors.initials: E
authors.lastname: Struys
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stockler-Ipsiroglu
authors.forename: Mary B
authors.initials: MB
authors.lastname: Connolly
mesh_terms: D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives / Q000172:deficiency / Q000235:genetics; D000140:Acidosis, Lactic / Q000175:diagnosis*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis*; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D020125:Mutation, Missense; D011736:Pyridoxine / Q000627:therapeutic use; D013702:Temporal Lobe / Q000473:pathology; D013788:Thalamus / Q000473:pathology
chemical_list: D000927:Anticonvulsants; D015074:2-Aminoadipic Acid; C000061:allysine; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine