title: Neonatal seizures and limb malformations associated with liver-specific complex IV respiratory chain deficiency.
abstract: An eight-week-old infant, the fourth child of consanguineous parents presented with intractable neonatal seizures. The mother had two previous miscarriages. The infant initially presented on day one with multifocal myoclonus, complex partial and generalised tonic-clonic seizures. On examination, there were dysmorphic hands and feet, with absent nails and terminal phalanges of the fingers and toes, hepatomegaly, marked axial and peripheral hypotonia and severe global developmental delay. Ophthalmological assessment showed 'salt and pepper' pigmentary retinopathy. The urinary organic acid profile revealed a marked increase in tricarboxylic acid metabolites. Urinary phosphate reabsorption was reduced at 84%. Type I fibre atrophy was seen on muscle histology, and a cytochrome c oxidase deficiency was found only on enzymology of liver tissue. Limb malformations associated with respiratory chain defects have rarely been reported. To our knowledge, this child has the most severe limb anomaly associated with a tissue-specific complex IV respiratory chain defect.
authors.affiliation: Department of Paediatric Neurology, The Children's University Hospital, Temple Street, Dublin, Ireland. mary.king@tsch.ie
authors.forename: M A
authors.initials: MA
authors.lastname: Kurian
authors.forename: E S
authors.initials: ES
authors.lastname: O'Mahoney
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.forename: E P
authors.initials: EP
authors.lastname: Treacy
authors.forename: M D
authors.initials: MD
authors.lastname: King
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D003241:Consanguinity; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D030401:Cytochrome-c Oxidase Deficiency / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D003937:Diagnosis, Differential; D003576:Electron Transport Complex IV / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics*; D017029:Epilepsy, Complex Partial / Q000175:diagnosis / Q000235:genetics; D004830:Epilepsy, Tonic-Clonic / Q000175:diagnosis / Q000235:genetics; D005385:Fingers / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D008099:Liver / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018832:Molecular Chaperones; D009123:Muscle Hypotonia / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D013226:Status Epilepticus / Q000175:diagnosis / Q000235:genetics; D014034:Toes / Q000002:abnormalities*; D014233:Tricarboxylic Acids / Q000652:urine
chemical_list: D008565:Membrane Proteins; D018832:Molecular Chaperones; C489345:SCO1 protein, human; D014233:Tricarboxylic Acids; D003576:Electron Transport Complex IV