Likely inborn error of metabolism

Gene: PAICS

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green - three unrelated cases with phosphoribosylaminoimidazole carboxylase deficiency, an inborn error of de novo purine synthesis caused by biallelic variants in the PAICS gene (PMID: 31600779; 39604553; 39726239)

Inclusion on this panel would also ensure inclusion on the Paediatric disorders super panel which is relevant to the polymalformative syndrome or neurodevelopmental disorder displayed by affected individuals.

Created: 27 Jan 2026, 12:25 p.m. | Last Modified: 27 Jan 2026, 12:25 p.m.

Panel Version: 8.91

Comment on phenotypes: OMIM phenotype (?Phosphoribosylaminoimidazole carboxylase deficiency, OMIM:619859) accessed on 27-01-2026

Created: 27 Jan 2026, 12:20 p.m. | Last Modified: 27 Jan 2026, 12:20 p.m.

Panel Version: 8.90

Pelet et al. 2019 (PMID: 31600779) report an AR inborn error of de novo purine synthesis due to homozygous missense variant in PAICS (c.158A>G; p.Lys53Arg) in 2 siblings from the Faroe islands. Catalytic activity of the mutant protein in patient skin fibroblasts was approx 10% of wild type levels. The siblings had multiple malformations resulting in early neonatal death.

Weng et al. 2024 (PMID: 39604553) identified two Taiwanese siblings with compound heterozygous variants, c.535T>C (p.Ser179Pro) and c.1207C>T (p.Arg403Ter). They presented a markedly different clinical course, with both being born at term following uncomplicated pregnancies. However, clinical manifestations did start to emerge from infancy and manifested as progressive cerebral atrophy, epileptic encephalopathy, psychomotor retardation, and retinopathy. Phenotypic variability could be attributed to residual enzyme activities where the Ser179Pro and Arg403Ter proteins had residual activities decreased to 76 and 21%, respectively, compared to 10% of the Lys35Arg protein of Faroe Island patients.

Boussion et al. 2025 (PMID: 39726239) reported a 7-year-old boy homozygous for the same p.Lys53Arg mutation as the Faroe cases. This individual presented with a multiple malformations including complex congenital heart disease, skeletal and esophageal defects but normal neurodevelopment. There was a similarly affected sibling with suspected PAICS deficiency, but this was not molecularly confirmed.
Sources: Literature

Created: 27 Jan 2026, 12:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Phosphoribosylaminoimidazole carboxylase deficiency, OMIM:619859

Publications

• 31600779
• 39604553
• 39726239