A novel homozygous variant causing fatal neonatal adenylosuccinate lyase (ADSL) deficiency presenting with respiratory failure and encephalopathy.

Neonatal adenylosuccinate lyase (ADSL) deficiency is a rare neurodegenerative disorder that is associated with epileptic encephalopathy, diffuse hypotonia, and respiratory failure. Loss of enzymatic function of ADSL leads to toxic buildup of succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). We describe a female term neonate who presented with respiratory failure and encephalopathy. Neuroimaging revealed microencephaly, a simplified gyral pattern, and diffuse white matter edema. Genetic testing showed novel homozygous loss of function mutations of ADSL, the adenylosuccinate lyase gene, consistent with fatal neonatal ADSL deficiency. We find this to be one of less than a dozen cases reported of the fatal neonatal phenotype of ADSL deficiency. The case highlights ADSL deficiency as a rare cause of neonatal encephalopathy and respiratory failure. Clinical recognition of epileptic encephalopathy, pertinent findings on MRI, and testing for S-Ado can confirm the diagnosis and support discussions about goals of care.