Anticipatory banking of samples enables diagnosis of adenylosuccinase deficiency following molecular autopsy in an infant with vacuolating leukoencephalopathy.

This study reports on a baby who died at 52 days old with severe brain problems and seizures. After death, doctors used advanced genetic testing and stored blood samples to diagnose a rare metabolic condition called adenylosuccinase deficiency. The brain showed unusual changes not previously linked to this condition. The parents were able to use this information for genetic counseling in their next pregnancy, which resulted in a healthy baby.

This case report describes a 52-day-old infant who died with severe epileptic encephalopathy and leukodystrophy. Post-mortem examination revealed unusual brain vacuolation. Molecular autopsy using clinical exome sequencing identified variants in the ADSL gene, leading to biochemical testing of stored samples that confirmed adenylosuccinase deficiency. Elevated succinyladenosine and succinylaminoimidazole carboxamide riboside levels were found in plasma, and fibroblast enzyme activity was only ~5% of normal.

This represents the first report of vacuolating leukodystrophy as a feature of adenylosuccinase deficiency. The parents successfully used genetic counseling for a subsequent pregnancy, resulting in an unaffected child. The case demonstrates the value of anticipatory sample banking for posthumous diagnosis.

This case expands the phenotypic spectrum of adenylosuccinase deficiency and highlights the diagnostic value of combining genomic analysis with biochemical testing. It emphasizes the importance of anticipatory sample banking in complex pediatric cases for potential posthumous diagnosis, which can inform genetic counseling and family planning decisions.

Single case report limits generalizability of findings. The novel brain changes observed may not be present in all cases of adenylosuccinase deficiency. Long-term outcomes and treatment implications cannot be assessed due to the fatal nature of this case.

Adenylosuccinase deficiency is a rare inborn error of metabolism. We present a newborn who died at 52 days of age with clinical features suggestive of severe epileptic encephalopathy and leukodystrophy of unknown cause. Post-mortem examination showed an unusual vacuolar appearance of the brain. A molecular autopsy performed via singleton clinical exome analysis revealed a known pathogenic and a variant of uncertain significance in ADSL that encodes adenylosuccinase.

Tests on previously stored plasma samples showed elevated succinyladenosine and succinylaminoimidazole carboxamide riboside levels. Adenylosuccinase activity in stored fibroblasts was only ~5% of control confirming the diagnosis of adenylosuccinase deficiency in the child. The parents opted for a chorionic villus biopsy in a subsequent pregnancy and had a child unaffected by adenylosuccinase deficiency. This report adds vacuolating leukodystrophy as a novel feature of adenylosuccinase deficiency and shows the power of biochemical investigations directed by genomic studies to achieve accurate diagnosis.

Importantly, this case demonstrates the importance of anticipatory banking of biological samples for reverse biochemical phenotyping in individuals with undiagnosed disorders who may not survive.