A Devastating Reminder: Refractory Neonatal Seizures, Hyperammonemia, and an ALDH7A1 Diagnosis

A neonatal case report describes multifocal seizures with severe metabolic instability and a confirmed ALDH7A1 pathogenic variant, stressing how urgent early recognition can be.

This report describes an infant with seizures starting on day three of life that did not respond to multiple antiseizure medications. The course included hepatomegaly, metabolic acidosis, elevated ammonia and lactate, and abnormal liver function tests, highlighting how PDE-ALDH7A1 can present as a systemic crisis, not “just seizures.”

Genetic testing identified a homozygous pathogenic ALDH7A1 variant, confirming PDE. Despite intensive management, the infant deteriorated and died, underscoring that delays or diagnostic uncertainty can have catastrophic consequences in some presentations.

From a scientific standpoint, this case emphasizes why PDE-ALDH7A1 is considered a biochemical emergency: the disorder can rapidly derail PLP-dependent neurotransmitter chemistry and seizure control, while the lysine-pathway metabolite load may also contribute to broader physiologic stress. It also reinforces the importance of considering PDE in consanguineous populations where autosomal recessive conditions are more common, and where earlier empiric pyridoxine (under medical supervision) plus confirmatory testing can be lifesaving.

Why this matters

It keeps the clinical urgency front and center: PDE is rare, but it is treatable, and time-to-treatment can matter.

Limitations

This is a single case report. It cannot predict outcomes for other infants, especially those diagnosed and treated earlier.

Sources

• “Neonatal Refractory Seizures and Hyperammonemia in a Neonate With ALDH7A1 Deficiency.” Clinical Case Reports (2025). DOI: 10.1002/ccr3.70852 (PubMed: 40919396; Free full text: PMC12411250)

Safety note: This summary is educational and not medical advice.