title: Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families.
abstract: OBJECTIVE
  To characterize a new lethal fetal and early postnatal variant of adenylosuccinate lyase (ADSL) deficiency.
  
  
  METHODS
  This was a retrospective analysis of 6 patients with very early presentation of ADSL deficiency.
  
  
  RESULTS
  Most of the 6 patients had impaired intrauterine growth, microcephaly, fetal hypokinesia, and a lack of fetal heart rate variability. Postnatally, they shared severe muscular hypotonia necessitating mechanical ventilation, intractable seizures, and early death. All 6 patients had biochemical evidence of severe (type 1) disease and low residual ADSL activities. All were compound heterozygous for mutations that, based on expression studies, have a pronounced effect on ADSL activity and/or stability.
  
  
  CONCLUSIONS
  ADSL deficiency may present with prenatal growth restriction, fetal and neonatal hypokinesia, and rapidly fatal neonatal encephalopathy. This clinical presentation is associated with genotypes resulting in very low residual enzyme activity.
authors.affiliation: Department of Pediatrics, Klinikum Neukölln, Berlin, Germany
authors.forename: Katharina
authors.initials: K
authors.lastname: Mouchegh
authors.forename: Marie
authors.initials: M
authors.lastname: Zikánová
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: Benno
authors.initials: B
authors.lastname: Kretzschmar
authors.forename: Thomas
authors.initials: T
authors.lastname: Kühn
authors.forename: Eva
authors.initials: E
authors.lastname: Mildenberger
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.forename: Jakub
authors.initials: J
authors.lastname: Krijt
authors.forename: Lenka
authors.initials: L
authors.lastname: Dvoráková
authors.forename: Tomás
authors.initials: T
authors.lastname: Honzík
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kmoch
authors.forename: Rainer
authors.initials: R
authors.lastname: Rossi
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D004247:DNA / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005313:Fetal Death / Q000201:enzymology / Q000209:etiology*; D005500:Follow-Up Studies; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D004247:DNA; D000264:Adenylosuccinate Lyase