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Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism that is classically attributed to defects in aldolase B. Although several studies evaluating the aldolase gene family have included ALDOC (HGNC:418) in their screening panels, no ALDOC‑specific variants or segregation data have been reported in HFI probands (PMID:8299883). This lack of direct genetic evidence keeps the role of ALDOC in HFI inconclusive despite its biochemical proximity to the better‐characterized ALDOB gene.
Similarly, functional assessments of the aldolase family have primarily focused on the effects of mutations in aldolase B on enzyme stability and substrate affinity. While some experimental studies have evaluated all isoforms, the data for ALDOC remain insufficient to demonstrate a pathogenic mechanism in HFI, thus limiting both its diagnostic and commercial utility. Key take‑home: Although ALDOC is a candidate within the aldolase family, current genetic and functional evidence does not support its routine use in the diagnosis or management of hereditary fructose intolerance.
Gene–Disease AssociationLimitedThe overall clinical evidence is limited owing to the absence of ALDOC‑specific variants or robust segregation data in HFI probands, with supporting data primarily derived from studies of ALDOB (PMID:8299883). Genetic EvidenceLimitedDespite inclusion in multi‑family screenings, no direct mutations in ALDOC have been documented in HFI cases, falling short of ClinGen genetic thresholds. Functional EvidenceLimitedFunctional studies have largely focused on aldolase B, and indirect assessments of ALDOC have not yielded conclusive data linking it to HFI pathogenesis (PMID:10229688). |