title: Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby.
abstract: BACKGROUND
  Molybdenum cofactor deficiency (MOCD) is a severe autosomal recessive neonatal metabolic disease that causes seizures and death or severe brain damage. Symptoms, signs and cerebral images can resemble those attributed to intrapartum hypoxia. In humans, molybdenum cofactor (MOCO) has been found to participate in four metabolic reactions: aldehyde dehydrogenase (or oxidase), xanthine oxidoreductase (or oxidase) and sulfite oxidase, and some of the components of molybdenum cofactor synthesis participate in amidoxime reductase. A newborn girl developed refractory seizures, opisthotonus, exaggerated startle reflexes and vomiting on the second day of life. Treatment included intravenous fluid, glucose supplementation, empiric antibiotic therapy and anticonvulsant medication. Her encephalopathy progressed, and she was given palliative care and died aged 1 week. There were no dysmorphic features, including ectopia lentis but ultrasonography revealed a thin corpus callosum.
  
  
  OBJECTIVE
  The aim of this study is to provide etiology, prognosis and genetic counseling.
  
  
  METHODS
  Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression.
  
  
  RESULTS
  Uric acid level was low in blood, and S-sulfo-L-cysteine and xanthine were elevated in urine. Compound Z was detected in urine. Two MOCS2 gene mutations were identified: c.501 + 2delT, which disrupts a conserved splice site sequence, and c.419C > T (pS140F). Protein expression studies confirmed that the p.S140F substitution was pathogenic. The parents were shown to be heterozygous carriers.
  
  
  CONCLUSIONS
  Mutation analysis confirmed that the MOCD in this family could not be treated with cPMP infusion, and enabled prenatal diagnosis and termination of a subsequent affected pregnancy.
authors.affiliation: Department of Paediatrics, Campbelltown Hospital, Campbelltown, NSW, Australia ; Department of Paediatrics, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Colbourne Pharmaceuticals GmbH, Viktoriaweg 7, 53859 Niederkassel, Germany ; University of Cologne, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Roeper
authors.affiliation: Department of Paediatrics, Campbelltown Hospital, Campbelltown, NSW, Australia ; Department of Paediatrics, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Allgood
authors.affiliation: Department of Paediatrics, Campbelltown Hospital, Campbelltown, NSW, Australia ; Department of Paediatrics, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Raymond
authors.initials: R
authors.lastname: Chin
authors.affiliation: Colbourne Pharmaceuticals GmbH, Viktoriaweg 7, 53859 Niederkassel, Germany ; University of Cologne, Germany.
authors.forename: Jose
authors.initials: J
authors.lastname: Santamaria
authors.affiliation: Monash Newborn, Level 5, 246 Clayton Road, Clayton, Victoria 3168, Australia ; The Ritchie Centre, Department of Paediatrics, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Flora
authors.initials: F
authors.lastname: Wong
authors.affiliation: Colbourne Pharmaceuticals GmbH, Viktoriaweg 7, 53859 Niederkassel, Germany ; University of Cologne, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Schwarz
authors.affiliation: Department of Paediatrics, Campbelltown Hospital, Campbelltown, NSW, Australia ; Department of Paediatrics, School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Whitehall
keywords: MOCS2A; Metabolic encephalopathy; Molybdenum cofactor deficiency