Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency:: Observation of 6 patients in 4 families

Objective. To characterize a new., lethal fetal and early postnatal variant of adenylosuccinate lyase (ADSL) deficiency. Study design. 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.