Urine metabolomic profiling in two siblings with biallelic pathogenic ATG7 variants with healthy control

ABSTRACT: Ultra-rare biallelic ATG7 variants were recently reported in five families presenting with neurodevelopmental disorders. Two adult female siblings (P1 and P2) from one family carried compound heterozygous loss-of-function variants (c.1975C>T [p.Arg659]; c.2080-2A>G, 39,40NM_006395.2), resulting in undetectable ATG7 protein in multiple tissues. This prompted us to test whether a congenital lack of ATG7 in humans might also cause tubular proteinuria and tubulopathy. While classical markers of PT injury (LCN2/NGAL) and tubular proteinuria (e.g., RBP, aminoaciduria) were absent in both siblings, P2 showed elevated urinary CC16 — a sensitive LMW PT dysfunction marker — compared to P1 and healthy controls. Urine metabolomic profiling revealed distinct metabolic signatures in both siblings relative to controls. Notably, P2 exhibited enrichment in pathways related to glucose, amino acid, and nucleotide metabolism, fatty acid degradation, the TCA cycle, and cancer metabolism, paralleling the metabolic abnormalities observed in ATG7-deficient preclinical models.

INSTRUMENT(S): Liquid Chromatography MS - negative - hilic-(hydrophilic-interaction-liquid-chromatography)-/-beh-amide

PROVIDER: MTBLS15856 | MetaboLights | 2026-09-30

REPOSITORIES: MetaboLights